interleukin-8 and Coronary-Artery-Disease

The association between interleukin-8 (IL-8) gene polymorphism -251 A>T and susceptibility to coronary artery disease (CAD) has been investigated previously; however, results remain controversial. Thus, a meta-analysis was conducted to reassess the effects of this polymorphism on CAD risks.. The PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies published up to December, 2018. The pooled odds ratios (OR) were calculated using STATA 13.0 software for allelic (A vs T) as well as homozygote (AA vs TT), heterozygote (AT vs TT), recessive (AA vs AT + TT), and dominant (AA + AT vs TT) genotype models, respectively.. Ten case-control studies (3744 cases and 3660 controls) were included. Overall, a significant association of IL-8 gene -251 A > T polymorphism with an increased risk of CAD was only observed in the dominant genotype model (OR = 1.48), but not others. In the subgroup analysis, significantly increased risks were also found for Chinese (OR = 1.64), polymerase chain reaction-restriction fragment length polymorphism genotyping (OR = 1.61), acute coronary syndrome (ACS) type (OR = 1.92 for 3 datasets; OR = 1.88 for 4 datasets), high quality (OR = 1.64), and age/gender matching status (OR = 1.55) under the dominant model. Furthermore, significantly increased risks were also found for ACS type under allelic (OR = 1.32 for 3 datasets; OR = 127 for 4 datasets), homozygote (OR = 1.64 for 3 datasets; OR = 1.50 for 4 datasets), heterozygote (OR = 1.32 for 3 datasets; OR = 1.30 for 4 datasets), and recessive (OR = 1.40 for 3 datasets; OR = 1.28 for 4 datasets) models.. This meta-analysis suggests that Chinese patients carrying -251A allele of IL-8 may have an increased risk for the development of CAD, especially ACS.

Topics: Acute Coronary Syndrome; Adult; Aged; Alleles; Asian People; Case-Control Studies; China; Coronary Artery Disease; Female; Genetic Predisposition to Disease; Genotype; Heterozygote; Homozygote; Humans; Interleukin-8; Male; Middle Aged; Odds Ratio; Polymorphism, Restriction Fragment Length

BACKGROUND Inflammation plays an important role in the pathogenesis of coronary artery disease (CAD). Studies have reported that inflammatory cytokine interleukin-8 (IL-8) gene -251 A/T (rs4073) polymorphism is correlated with CAD susceptibility, but the result remains controversial. The objective of this study was to clarify the association between IL-8 gene -251 A/T polymorphism and CAD risk. MATERIAL AND METHODS A meta-analysis included 8244 patients from 9 individual studies with 10 populations was conducted. Heterogeneity test was conducted, and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated used fixed-effect or random-effects model accordingly. Publication bias was evaluated with the Begg's funnel plot and Egger's test. Sensitivity analysis was also conducted. RESULTS A significant association between IL-8 gene -251 A/T polymorphism and CAD risk was found in the dominant model (OR 1.42, 95% CI 1.16-1.76, P<0.001), recessive model (OR 1.30, 95% CI 1.12-1.52, P<0.001), allelic model (OR 1.28, 95% CI 1.12-1.47, P<0.001), homozygote model (OR 1.59, 95% CI 1.21-2.08, P<0.001), and heterozygote model (OR 1.35, 95% CI 1.11-1.64, P=0.002). Subgroup analysis by ethnicity found significant associations in the Chinese population in the dominant model(OR 1.43, 95% CI 1.26-1.61, P<0.001), recessive model (OR 1.39, 95% CI 1.21-1.59, P<0.001), allelic model (OR 1.31, 95% CI 1.21-1.42, P<0.001), homozygote model (OR 1.66, 95% CI 1.41-1.95, P<0.001), and heterozygote model (OR 1.34, 95% CI 1.18-1.52, P<0.001), but no significant association was found in the Caucasian population. No significant publication bias was found. CONCLUSIONS The IL-8 gene -251 A/T polymorphism was significantly associated with CAD risk in the Chinese population but not in the Caucasian population, -251 A allele carrier had an increased risk of CAD in the Chinese population.

Topics: Alleles; Asian People; China; Coronary Artery Disease; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-8; Odds Ratio; Polymorphism, Single Nucleotide; White People

Several reports have suggested a possible association between the interleukin (IL)-8-251A/T single-nucleotide polymorphism (SNP) and the susceptibility to coronary artery disease (CAD). Due to inconclusive results of the studies so far, we conducted a meta-analysis to systematically summarize the studies on the association between this SNP and CAD risk. A systematic literature search identified 9 case-control studies (3752 cases and 4219 controls) on the IL-8-251A/T polymorphism. We observed a significant association between different genetic forms of -251A/T SNP and CAD risk, like the allele model (A vs T: odds ratio [OR] 1.14, 95% confidence interval [CI] 1.02-1.27, P = .02), dominant model (AA + AT vs TT: OR 1.20, 95% CI 1.01-1.43, P = .042), recessive model (AA vs AT + TT: OR 1.15, 95% CI 1.03-1.27, P = .01), and homozygous model (AA vs TT: OR 1.26, 95% CI 1.01-1.56, P = .037), whereas the heterozygote model did not show any significant association (AT vs TT: OR 1.16, 95% CI 0.98-1.38, P = .091). Furthermore, significant heterogeneity was observed among studies in terms of all genetic models, except the recessive model. Analysis of the ethnic subgroups revealed a significantly higher risk of CAD in the East Asian population carrying this SNP, and the heterogeneity among the studies regarding the East Asian population was decreased after subgroup analysis. The results of this meta-analysis suggest that the IL-8-251A/T SNP may increase the risk of CAD, especially in people of East Asian ethnicity. Further large-scale, multicenter epidemiological studies are warranted to validate this finding.

Topics: Case-Control Studies; Coronary Artery Disease; Ethnicity; Genetic Predisposition to Disease; Humans; Interleukin-8; Polymorphism, Single Nucleotide

This study aimed to evaluate the role of off-pump coronary artery bypass (CAB) surgery on the decrease of postoperative inflammatory responses in patients. We systematically searched databases of PubMed and Embase to select the related studies. Interleukin (IL) 6, 8, and 10 were used as outcomes and pooled analysis was performed using R 3.12 software. Standardized mean differences (SMDs) and their 95% confidence intervals (95% CIs) were considered as effect estimates. A total of 27 studies, including 1340 participants, were recruited in this meta-analysis. The pooled analyses showed that postoperative concentration of IL-10 at 12 hours was significantly lower in off-pump CAB group compared to on-pump CAB group (SMD = -1.3640, 95% CI = -2.0086--0.7193). However, no significant differences were found in pre and postoperative concentrations of IL-6 and 8 between off-pump and on-pump CAB groups. These results suggest that there is no advantage of off-pump CAB surgery in the reduction of inflammation compared to on-pump CAB surgery.

Topics: Aged; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Coronary Artery Disease; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Middle Aged; Postoperative Complications; Postoperative Period; Time Factors

Low-grade inflammation is central to coronary artery disease (CAD) and type 2 diabetes (T2D) and is reduced by exercise training. The objective of this study was to compare the anti-inflammatory potential of moderate-to-vigorous intensity continuous training (MICT) and high-intensity interval training (HIIT) in patients with CAD with or without T2D. The design and setting of this study is based on a secondary analysis of registered randomized clinical trial NCT02765568. Male patients with CAD were randomly assigned to either MICT or HIIT, with subgroups divided according to T2D status (non-T2D-HIIT n = 14 and non-T2D-MICT n = 13; T2D-HIIT n = 6 and T2D-MICT n = 5). The intervention was a 12-week cardiovascular rehabilitation program consisting of either MICT or HIIT (twice weekly sessions) and circulating cytokines measured pre- and post-training as inflammatory markers. The co-occurrence of CAD and T2D was associated with increased plasma IL-8 (p = 0.0331). There was an interaction between T2D and the effect of the training interventions on plasma FGF21 (p = 0.0368) and IL-6 (p = 0.0385), which were further reduced in the T2D groups. An interaction between T2D, training modalities, and the effect of time (p = 0.0415) was detected for SPARC, with HIIT increasing circulating concentrations in the control group, while lowering them in the T2D group, and the inverse occurring with MICT. The interventions also reduced plasma FGF21 (p = 0.0030), IL-6 (p = 0.0101), IL-8 (p = 0.0087), IL-10 (p < 0.0001), and IL-18 (p = 0.0009) irrespective of training modality or T2D status. HIIT and MICT resulted in similar reductions in circulating cytokines known to be increased in the context of low-grade inflammation in CAD patients, an effect more pronounced in patients with T2D for FGF21 and IL-6.

Topics: Coronary Artery Disease; Cytokines; Diabetes Mellitus, Type 2; Exercise; High-Intensity Interval Training; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Pilot Projects

Coronary artery bypass grafting with cardiopulmonary bypass (CPB) induces an inflammatory reaction that is associated with postoperative complications. Influenza vaccination has been shown to decrease cardiovascular morbidity in patients with cardiovascular disease, possibly via its anti-inflammatory properties. We hypothesize that influenza vaccination would attenuate the inflammatory reaction after CPB.. Thirty patients undergoing coronary artery bypass grafting were blindly randomized to receive the influenza vaccine (group I, n = 15) or a placebo (group II, n = 15) preoperatively. Serum samples of proinflammatory mediators (interleukin-6, interleukin-8, tumor necrosis factor, C-reactive protein) as well as the anti-inflammatory interleukin-10 were collected at different time points perioperatively. Assessment of myocardial dysfunction was investigated by measuring hemodynamic data, echocardiographic data, and troponin levels. Other clinical outcomes were collected prospectively.. Proinflammatory cytokine levels were significantly reduced in the treatment group vs the placebo group (interleukin-6 [157.4 pg/dL vs 256 pg/dL, P = .043], interleukin-8 [65.03 pg/dL vs 118.56 pg/dL, P = .025], and tumor necrosis factor [12.05 pg/dL vs 20.8 pg/dL, P = .003]). These differences were observed at the end of CPB and persisted for 2 days postoperatively. Interestingly, the level of the anti-inflammatory marker interleukin-10 was significantly higher in group I (83.3 pg/dL vs 15.15 pg/dL, P = .008). Evidence of improved myocardial protection was observed in group I, as reflected by troponin measurements postoperatively (6020.2 pg/dL vs 12,098.01 pg/dL, P = .052).. Influenza vaccination attenuates the inflammatory response to CPB as reflected by a reduction in the level of troponin and proinflammatory mediators and an increase in the anti-inflammatory cytokine interleukin-10.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Artery Disease; Double-Blind Method; Female; Humans; Influenza Vaccines; Interleukin-6; Interleukin-8; Male; Middle Aged; Pilot Projects; Postoperative Complications; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

Obstructive sleep apnea (OSA) and enhanced vascular inflammation coexist in patients with coronary artery disease (CAD). Continuous positive airway pressure (CPAP) is first-line treatment for OSA with daytime sleepiness. This analysis of data from the RICCADSA (Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnea) trial investigated the effects of CPAP on inflammatory markers in patients with CAD and nonsleepy OSA.. This single-center, randomized, controlled, open-label trial enrolled consecutive revascularized patients with nonsleepy OSA (apnea-hypopnea index >15/h; Epworth Sleepiness Scale score <10). Levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were measured in blood samples taken at baseline (median 94 days after revascularization) and after 1 year of follow-up in patients randomized to CPAP or no-CPAP.. A total of 220 patients with analyzable blood samples at baseline and 1 year were included. Baseline IL-6 levels were significantly lower in the CPAP versus no-CPAP group (median 3.1 pmol/L [interquartile range 1.3-5.7] vs. 4.2 pmol/L [2.0-8.9], respectively; p = .005). At 1-year follow-up, median IL-6 levels were significantly reduced in both groups (to 2.2 pmol/L [1.2-3.9] in the CPAP group and to 2.2 [1.2-4.7] in no-CPAP group; both p < .001 vs. baseline). IL-8, hs-CRP, and TNF-α did not change significantly from baseline. There was no association between CPAP adherence and changes in inflammatory marker levels.. In patients with stable CAD and nonsleepy OSA, inflammatory biomarkers did not change significantly over time except for IL-6 levels, which reduced to the same extent in the CPAP and no-CPAP groups.. ClinicalTrials.gov, ID: NCT00519597; researchweb.org, VGSKAS-4731.

Topics: Aged; Biomarkers; C-Reactive Protein; Continuous Positive Airway Pressure; Coronary Artery Disease; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Sleep Apnea, Obstructive; Sleep Stages; Tumor Necrosis Factor-alpha

Trimetazidine (TMZ) exhibits metabolic and cardioprotective effects. The aim of this study was to assess the effects of TMZ on interleukin-2 (IL-2) and interleukin-8 (IL-8) serum concentrations in 156 patients with stable coronary artery disease. They underwent a treadmill exercise test (TET) before and after 3 months of TMZ treatment. IL-2 and IL-8 concentrations were determined before and after each TET. Before treatment, TET did not influence IL-2 concentrations, whereas IL-8 concentrations increased. TMZ treatment led to a decrease in IL-2 concentrations before TET, as well as it prevented the increase of IL-8 following the second TET. Obtained results confirmed the improvement in TET performance during TMZ treatment and they revealed a significant influence of TMZ on IL-2 and IL-8 concentrations both before and after TET. These changes may reflect potential anti-inflammatory effects of TMZ.

Topics: Adult; Coronary Artery Disease; Exercise; Female; Humans; Interleukin-2; Interleukin-8; Male; Middle Aged; Stress, Physiological; Trimetazidine

The minimized extracorporeal circulation system (MECC) is being used to reduce priming volume and blood/polymer contact during cardiac procedures. In this study, we evaluated the efficacy and potential advantages of the system in coronary artery bypass graft (CABG) patients. We included two groups of patients destined for CABG in a prospective, randomized study: Group A was operated on the usual pump (n = 30) while Group B was operated using the MECC (n = 50). Pre-operative demographics, intra-operative times and values as well as a series of post-operative outcome data (blood loss, transfusion requirements, ventilation time, ICU and hospital stay) were recorded. CK, CK-MB, troponin-T, IL-6 and IL-8 were measured. Pre-operative and post-operative lung function were assessed. In the MECC-operated group, patients developed less post-operative troponin-T (0.2 +/- 0.3 vs. 0.5 +/- 0.5 ng/mL, p=0.031) and less IL-8 (13.8 +/- 5 vs. 22.5 +/- 0.5 microg/L, p = 0.05). While blood loss was comparable in both groups, packed red blood cells and fresh frozen plasma were given less frequently in the MECC group (p = 0.015 resp. 0.022). The one-tailed Student's t-test revealed shorter bypass time in the MECC group (74 +/- 17 vs. 82 +/- 24 min). There was no difference in ventilation and ICU-time (patients were not treated in a fast-track fashion). The FEV1 was better in the MECC group (relative values: 70.1 +/- 18.2% vs. 61.1 +/- 12.3%, p = 0.02). Utilization of the MECC may cause less cytokine (IL-8) liberation, owing to less blood/tubing contact, as well as less red blood cell and fresh frozen plasma demand. It may also be the circuit in patients with chronic obstructive pulmonary disease (COPD).

Topics: Aged; Coronary Artery Bypass; Coronary Artery Disease; Creatine Kinase; Creatine Kinase, MB Form; Extracorporeal Circulation; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Prospective Studies; Troponin T

The aim of this study was to investigate the effect of systemic CPB temperature on the production of the key mediators of the systemic inflammatory response to coronary artery bypass graft (CABG) surgery.. Randomized clinical study.. University hospital.. Thirty patients undergoing first-time CABG surgery.. The patients were randomized to hypothermic (32 degrees C, n = 15) or normothermic (36 degrees C, n = 15) CPB.. Plasma interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), cortisol, and neutrophils were measured the day before operation, at closure of the sternum, and 4, 16, and 44 hours later. The cytokine, CRP, cortisol, and neutrophil responses were independent of temperature during CPB with peak concentrations of IL-10 at closure of the sternum followed by IL-6, IL-8, cortisol, neutrophils, and finally CRP. A correlation between maximal plasma concentrations of IL-10 and cortisol was seen in both groups after surgery (p = 0.02). Drainage after surgery was lower after normothermic CPB (p=0.02), with no difference in the requirement for blood transfusion. All patients were discharged from the intensive care unit within 24 hours after surgery.. The release of systemic inflammatory mediators after cardiac surgery was independent of mild hypothermia (32 degrees C) versus normothermia (36 degrees C) during CPB.

Topics: Adult; Aged; Biomarkers; Body Temperature; C-Reactive Protein; Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Artery Disease; Female; Humans; Hydrocortisone; Hypothermia, Induced; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Neutrophils; Research Design; Time Factors; Treatment Outcome

Inflammatory pathways are involved in destabilization of atherosclerotic plaques. We assessed the hypothesis that endurance training decreases circulating concentrations of inflammatory markers in persons with coronary artery disease (CAD) and cardiovascular risk factors (CVRFs). Thirty-two subjects with CAD and/or CVRFs joined a 12-week supervised endurance training. We found a significant decrease of the chemokines interleukin (IL)-8 (pre: 3.9+/-0.6, change: -1.2+/-0.4 pg/ml, -21%, p=0.002) and monocyte chemoattractant protein-1 (pre: 213+/-9, change: -20.4+/-8.2 pg/ml, -5%, p=0.03). Diabetes mellitus (DM) significantly influenced changes of IL-8 (p=0.002). IL-8 substantially dropped by 39% in diabetics. Moreover, matrix metalloproteinase-9 (MMP-9) highly significantly decreased in response to training (pre: 750+/-98, change: -278+/-77 ng/ml, -18%, p=0.005). Exercise-induced changes of MMP-9 were influenced by concomitant use of statins (p=0.038). We observed a particularly strong MMP-9 reduction of 44% in patients treated with statins. Acute phase reactants IL-6 (pre: 1.7+/-0.3, change: +0.25+/-0.7 pg/ml, +4%, p=0.58) and high sensitivity C-reactive protein (pre: 2.1+/-0.5, change: -0.25+/-0.4 mg/l, -9%, p=0.54) did not change in response to training. In conclusion, endurance training decreased circulating chemokines and MMP-9, which may in part explain its beneficial effect on coronary risk. Patients with DM or treated with statins because of hypercholesterolemia may particularly take advantage.

Topics: Chemokine CCL2; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Exercise Therapy; Female; Follow-Up Studies; Humans; Inflammation; Interleukin-8; Male; Matrix Metalloproteinase 9; Middle Aged; Physical Endurance; Prognosis; Prospective Studies; Risk Factors; Severity of Illness Index

We investigated whether pro-inflammatory aspects of the postprandial phase can be modulated by rosuvastatin in premature coronary artery disease (CAD) patients. Herefore standardized 8 h oral fat loading tests were performed off-treatment and after rosuvastatin 40 mg/d in 20 male CAD patients (50 +/- 4 years). The expression of leukocyte activation markers CD11a, CD11b, CD62L and CD66b was studied using flowcytometry. Migration of isolated neutrophils towards chemoattractants was determined in a fluorescence-based assay. Rosuvastatin did not affect baseline leukocyte counts nor the postprandial neutrophil increment (maximum mean increase +10% pre- and +14% post-treatment, P < 0.01 for each). Rosuvastatin reduced baseline platelets (from 266 +/- 78 to 225 +/- 74 x 10(9) cells/L, P < 0.001) and blunted the postprandial platelet count change (maximum mean increase +6%, P = 0.01, and 0%, respectively). The baseline expression of CD11a, CD11b and CD62L increased on most types of leukocytes by rosuvastatin, whereas the postprandial responses were unaffected. Pretreatment, postprandial neutrophil migration increased dose-dependently, but there were no postprandial changes after rosuvastatin. The latter effect was unrelated to changes in lipoprotein concentrations. In conclusion, in CAD patients postprandial pro-inflammatory and pro-coagulant changes can be modified by rosuvastatin. These apparently lipid-lowering independent effects may render protection against atherosclerosis.

Topics: Adult; Antigens, CD; CD11a Antigen; CD11b Antigen; Cell Adhesion Molecules; Chemotaxis, Leukocyte; Coronary Artery Disease; Dietary Fats; Erythrocyte Count; Fluorobenzenes; GPI-Linked Proteins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Interleukin-8; L-Selectin; Leukocytes; Male; Middle Aged; Neutrophils; Oxidative Stress; Platelet Count; Postprandial Period; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Vascular Cell Adhesion Molecule-1

Recent data derived primarily from studies in animal models suggest that fractalkine (CX3CL1) and its cognate receptor, CX3CR1, play a role in atherogenesis. We, therefore, hypothesized that enhanced CX3CL1/CX3CR1 expression may promote atherogenesis in patients with coronary artery disease (CAD).. We examined the plasma levels of CX3CL1 and CX3CR1 expression in peripheral blood mononuclear cells (PBMC) in various CAD populations (30 patients with previous myocardial infarction, 40 patients with stable angina, 40 patients with unstable angina, and a total of 35 controls) and used various experimental approaches to characterize CX3CL1-mediated leukocyte responses. We found that the plasma levels of CX3CL1 are greatly increased in CAD, particularly in unstable disease. The parallel increase of CX3CR1 expression in PBMC was predominantly attributable to an expansion of the (CX3CR1+)(CD3+)(CD8+) T cell subset and was associated with enhanced chemotactic, adhesive, and inflammatory responses to CX3CL1. Statin therapy for 6 months reduced the expression of CX3CL1 and CX3CR1, reaching statistical significance for both parameters only during aggressive (atorvastatin, 80 mg qd) but not conventional (simvastatin, 20 mg qd) therapy. Consequently, the functional responses of the PBMC to CX3CL1 including migration, adhesion, and secretion of interleukin-8 were attenuated by the treatments.. Our results suggest that the CX3CL1/CX3CR1 dyad may contribute to atherogenesis and plaque destabilization in human CAD.

Topics: Angina, Unstable; Atorvastatin; Cell Adhesion; Cells, Cultured; Chemokine CX3CL1; Chemokines, CX3C; Chemotaxis; Cholesterol, LDL; Coronary Artery Disease; CX3C Chemokine Receptor 1; Endothelium, Vascular; Gene Expression; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-8; Leukocytes, Mononuclear; Membrane Proteins; Myocardial Infarction; Pyrroles; Receptors, Chemokine; Simvastatin; Umbilical Veins

Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8 play a key role in the inflammatory cascade after cardiopulmonary bypass (CPB) and may induce cardiac and lung dysfunction. Antiinflammatory cytokines such as IL-10 may also significantly limit these complications. Corticosteroid administration before CPB increases blood IL-10 levels and prevents proinflammatory cytokine release. This study examined the association of increased release of IL-10, stimulated by steroid pretreatment, with reduced myocardial and lung injury after CPB.. Twenty patients undergoing coronary artery bypass grafting (CABG) received either preoperative steroid (n = 10, protocol group) or no steroid (n = 10, control group). Perioperative care was standardized, and all caregivers were blinded to treatment group. Seven intervals of blood samples were obtained and assayed for TNF-alpha, IL-6, IL-8, and IL-10. Various hemodynamic and pulmonary measurements were obtained perioperatively. Levels of MB isoenzyme creatine kinase (CK-MB) were also measured.. In the protocol group, proinflammatory cytokines were significantly reduced while IL-10 levels were much higher after CPB. The protocol group had a lower alveolar-arterial oxygen gradient and higher ratio of arterial oxygen pressure to fraction of inspired oxygen after CPB. Creatine kinase (CK) and CK-MB were reduced in the patients treated with steroid. Correlations were found between plasma cytokines levels and cardiac index, and CK-MB.. This study confirms that corticosteroids abolish proinflammatory cytokines release and increase blood IL-10 levels after CPB. Our findings demonstrate a greater release of IL-10 induced by steroid pretreatment, and better heart and lung protection after CPB.

Topics: Aged; Analysis of Variance; Biomarkers; Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Artery Disease; Cytokines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Lung Diseases; Lung Injury; Male; Middle Aged; Myocardial Reperfusion Injury; Postoperative Period; Predictive Value of Tests; Preoperative Care; Prognosis; Prospective Studies; Reference Values; Risk Assessment; Statistics, Nonparametric; Steroids; Treatment Outcome; Tumor Necrosis Factor-alpha

Atherosclerosis can to a certain extent be regarded as an inflammatory disease. Also, inflammatory markers may provide information about cardiovascular risk. Whether macrolide antibiotics, especially clarithromycin, have an anti-inflammatory effect in patients with atherosclerosis is not exactly known. To study this phenomenon, a placebo-controlled, randomized, double-blind study was performed. A total of 231 patients with documented coronary artery disease received a daily dose of either 500 mg of slow-release clarithromycin or placebo until the day of surgery. Levels of inflammatory markers (C-reactive protein, interleukin-2 receptor [IL-2R], IL-6, IL-8, and tumor necrosis factor alpha) were assessed during the preoperative outpatient visit, on the day of surgery, and 8 weeks after surgery. Also, changes in the levels of inflammatory markers between visits were determined by delta calculations. Baseline patient characteristics were balanced between the two treatment groups: the average age was 66 years (standard deviation [SD] = 9.0), 79% of the patients were male, and the average number of tablets used was 16 (SD = 9.3). The inflammatory markers of the groups as well as the delta calculations were not significantly changed. Treatment with clarithromycin did not influence the inflammatory markers in patients with atherosclerosis.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; C-Reactive Protein; Clarithromycin; Coronary Artery Bypass; Coronary Artery Disease; Double-Blind Method; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Prospective Studies; Receptors, Interleukin-2; Treatment Failure; Tumor Necrosis Factor-alpha

A single high-fat meal induces endothelial activation, which is associated with increased serum concentrations of inflammatory cytokines.. We compared the effect of 3 different meals on circulating concentrations of interleukin 8 (IL-8), interleukin 18 (IL-18), and adiponectin in healthy subjects and in patients with type 2 diabetes mellitus.. Thirty patients with newly diagnosed type 2 diabetes and 30 matched, nondiabetic subjects received the following 3 isoenergetic (780 kcal) meals separated by 1-wk intervals: a high-fat meal; a high-carbohydrate, low-fiber (4.5 g) meal; and a high-carbohydrate, high-fiber meal in which refined-wheat flour was replaced with whole-wheat flour (16.8 g). We analyzed serum glucose and lipid variables and serum IL-8, IL-18, and adiponectin concentrations at baseline and at 2 and 4 h after ingestion of the meals.. Compared with nondiabetic subjects, diabetic patients had higher fasting IL-8 (P < 0.05) and IL-18 (P < 0.01) concentrations and lower adiponectin concentrations (P < 0.01) at baseline. In both nondiabetic and diabetic subjects, IL-18 concentrations increased and adiponectin concentrations decreased (P < 0.05) from baseline concentrations after consumption of the high-fat meal. After consumption of the high-carbohydrate, high-fiber meal, serum IL-18 concentrations decreased from baseline concentrations (P < 0.05) in both nondiabetic and diabetic subjects; adiponectin concentrations decreased after the high-carbohydrate, low-fiber meal in diabetic patients. IL-8 concentrations did not change significantly after consumption of any of the 3 meals.. This study provides evidence that circulating IL-18 and adiponectin concentrations are modulated by familiar foodstuffs in humans. Meal modulation of cytokines involved in atherogenesis may represent a safe strategy for ameliorating atherogenetic inflammatory activity in diabetic patients.

Topics: Adiponectin; Adult; Blood Glucose; Coronary Artery Disease; Cross-Over Studies; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Female; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-18; Interleukin-8; Male; Proteins

Inflammation has been shown to be an important feature of atherosclerosis. We aimed to assess a profile of inflammatory cytokines and growth factors in patients with established coronary artery disease (CAD), 12 months after stent implantation.. A total of 193 patients with CAD, who were candidates for angiography, 12 months after stent implantation (cases), were compared with 107 patients with CAD, who were candidates for their first angiography (controls). Fasting blood glucose (FBG), triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and high-sensitive C-reactive protein (hs-CRP) were measured using routine methods. The serum concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, MCP-1, EGF and VEGF were determined using competitive chemiluminescence immunoassays.. Serum levels of FBG (. In patients with CAD and higher consumption of drug used (statins, aspirin and glucose lowering agents) to mitigate the risk of a secondary event, the level of hs-CRP one year after stent implantation decreased despite of significant higher serum levels of pro- and anti-inflammatory cytokines and growth factors.

Topics: Angiography; C-Reactive Protein; Cholesterol; Coronary Artery Disease; Cytokines; Epidermal Growth Factor; Humans; Interleukin-2; Interleukin-4; Interleukin-8; Stents; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Sparse data assessed the association of apolipoprotein A1 (ApoA1) and high density lipoprotein cholesterol (HDL-C) with inflammation. We investigated this association in a hospital-based cross-sectional pilot study that included 7296 patients with coronary artery disease (CAD). In multivariate analysis, negative associations of ApoA1 and HDL-C with C-reactive protein (CRP), high sensitivity CRP (hsCRP), and tumor necrosis factor-α (TNF-α) were shown. The corresponding CRP, hsCRP, and TNF-α values were 5.28 (vs 11.70 mg/L), 4.50 (vs 11.50 mg/L), and 7.68 (vs 10.90 pg/mL) for ApoA1, and 7.13 (vs 10.60 mg/L), 6.27 (vs 9.19 mg/L), and 8.11 (vs 11.86 pg/mL) for HDL-C in the fourth quartiles compared with the first quartiles. ApoA1/HDL-C ratio was inversely associated with hsCRP and interleukin-6 (IL-6). No significant associations of ApoA1 and HDL-C with IL-6 and IL-8, and of ApoA1/HDL-C ratio with CRP, IL-8, and TNF-α were observed. In path analyses, there was no evidence of mediating effects of body mass index on the "ApoA1 and HDL-C-inflammation" relationship. Generally, our study of CAD patients identified graded and inverse associations of ApoA1, HDL-C, and ApoA1/HDL-C ratio with inflammatory marker (CRP, hsCRP, IL-6, IL-8, or TNF-α) levels.

Topics: Adult; Apolipoprotein A-I; Apolipoproteins B; C-Reactive Protein; Cholesterol, HDL; Coronary Artery Disease; Cross-Sectional Studies; East Asian People; Humans; Inflammation; Interleukin-6; Interleukin-8; Pilot Projects; Tumor Necrosis Factor-alpha

Anti-aging protein Klotho has been reported to be associated with atherosclerosis, which was considered as a chronic inflammatory disease. However, the relationship between Klotho and senile inflammation remained unclear. The present study aims to ascertain the correlation of Klotho with inflammation in middle-aged and elderly coronary atherosclerotic disease (CAD).. A total of 302 patients with CAD were included in this study. Coronary atherosclerosis was confirmed and quantified for all patients by coronary angiography. Serum Klotho was detected by enzyme linked immunosorbent assay. Serum concentrations of IL-6 and IL-8 were quantified by chemiluminescence assay. T-lymphocyte subsets were measured using flow cytometry.. Multivariate linear regression analysis showed that serum Klotho was an independent predictor for circulating monocytes (standard β = -0.321, P < 0.001) and CD4+/CD8+ ratio (standard β = -0.522, P < 0.001). After adjustment, serum Klotho was still independently associated with IL-6 (standard β = -0.395, P < 0.001) and IL-8 (standard β = -0.296, P < 0.001). Moreover, circulating monocytes, CD4+ and CD8+ lymphocytes were correlated with increased serum concentrations of IL-6 and IL-8, independent of CRP (P < 0.05). In receiver operating characteristic curve analysis, CD4+/CD8+ ratio (AUC = 0.863, P < 0.001), IL-6 (AUC = 0.893, P < 0.001) and IL-8 (AUC = 0.884, P < 0.001) presented the excellent predictive performance for significant CAD.. Decreased concentrations in serum Klotho reflect senile inflammation, which is related to the severity of CAD in middle-aged and elderly patients.

Topics: Aged; Aging; Atherosclerosis; Coronary Angiography; Coronary Artery Disease; Humans; Inflammation; Interleukin-6; Interleukin-8; Middle Aged

The current research aimed to expound the genes and pathways that are involved in coronary artery disease (CAD) and ischaemic stroke (IS) and the related mechanisms.. Two array CAD datasets of (GSE66360 and GSE97320) and an array IS dataset (GSE22255) were downloaded. Differentially expressed genes (DEGs) were identified using the limma package. The online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) (version 6.8; david.abcc.ncifcrf.gov) was used to annotate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses of the DEGs. A protein-protein interaction (PPI) network was constructed by Cytoscape software, and then Molecular Complex Detection (MCODE) analysis was used to screen for hub genes. The hub genes were also confirmed by RT-qPCR and unconditional logistic regression analysis in our CAD and IS patients.. A total of 20 common DEGs (all upregulated) were identified between the CAD/IS and control groups. Eleven molecular functions, 3 cellular components, and 49 biological processes were confirmed by GO enrichment analysis, and the 20 common upregulated DEGs were enriched in 21 KEGG pathways. A PPI network including 24 nodes and 68 edges was constructed with the STRING online tool. After MCODE analysis, the top 5 high degree genes, including Jun proto-oncogene (JUN, degree = 9), C-X-C motif chemokine ligand 8 (CXCL8, degree = 9), tumour necrosis factor (TNF, degree = 9), suppressor of cytokine signalling 3 (SOCS3, degree = 8) and TNF alpha induced protein 3 (TNFAIP3, degree = 8) were noted. RT-qPCR results demonstrated that the expression levels of CXCL8 were increased in IS patients than in normal participants and the expression levels of SOCS3, TNF and TNFAIP were higher in CAD/IS patients than in normal participants. Meanwhile, unconditional logistic regression analysis revealed that the incidence of CAD or IS was positively correlated with the CXCL8, SOCS3, TNF and TNFAIP3.. The CXCL8, TNF, SOCS3 and TNFAIP3 associated with inflammation may serve as biomarkers for the diagnosis of CAD or IS. The possible mechanisms may involve the Toll-like receptor, TNF, NF-kappa B, cytokine-cytokine receptor interactions and the NOD-like receptor signalling pathways.

Topics: Biomarkers; Brain Ischemia; Coronary Artery Disease; Female; Humans; Inflammation; Interleukin-8; Logistic Models; Male; Protein Interaction Mapping; Proto-Oncogene Mas; Real-Time Polymerase Chain Reaction; Suppressor of Cytokine Signaling 3 Protein; Tumor Necrosis Factor alpha-Induced Protein 3

Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators were involved in the pathogenesis of atherosclerosis. This study sought to investigate the effects of proatherogenic inflammatory and antiatherogenic inflammatory mediators on the proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations. We measured the expression levels of proatherogenic inflammatory/antiatherogenic inflammatory cytokines. This included interleukin-1

Topics: Aged; Aged, 80 and over; Angina Pectoris; C-Reactive Protein; Coronary Artery Disease; Cytokines; Female; Humans; Interleukin-1; Interleukin-10; Interleukin-13; Interleukin-6; Interleukin-8; Male; Multivariate Analysis; Myocardial Ischemia; Tumor Necrosis Factor-alpha

This study aimed to investigate the association between inflammation-related microRNAs (miR-21, 146a, 155) and the plaque stability in coronary artery disease patients.. The expression of miR-21, 146a, and 155 was measured by real-time PCR in 310 consecutive patients. The level of hs-CRP, IL-6, and IL-8 was measured by ELISA. The plaque stability of coronary stenotic lesions was evaluated with intravascular ultrasound (IVUS).. (1) The levels of hs-CRP, IL-6, and IL-8 were significantly increased in the UAP and AMI groups compared with the CPS group (. The expression of miR-21 and miR-146a are associated with the plaque stability in coronary stenotic lesions, whereas miR-155 expression is inversely associated with the plaque stability.

Topics: C-Reactive Protein; Coronary Artery Disease; Coronary Stenosis; Female; Humans; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; MicroRNAs; Middle Aged; Plaque, Atherosclerotic; Real-Time Polymerase Chain Reaction; Ultrasonography, Interventional

Topics: Adult; Aged; Coronary Artery Disease; Female; Genetic Predisposition to Disease; Humans; India; Interleukin-10; Interleukin-8; Male; Middle Aged; Polymorphism, Single Nucleotide

Normalized optical density (NOD) measured by optical coherence tomography represents neointimal maturity after coronary stent implantation and is correlated with morphologic information provided by both light and electron microscopy. We aimed to test the hypothesis that even second generation drug-eluting stents (DESs) are problematic in terms of neointimal maturity. We implanted bare-metal stents (BMS: n = 14), everolimus-eluting stents (EESs: n = 15) or zotarolimus-eluting stents (ZESs: n = 12) at 41 sites in 32 patients with stable coronary artery disease. OCT was performed at up to 12 months of follow-up, and the average optical density of neointima covering struts was evaluated. NOD was calculated as the optical density of stent-strut covering tissue divided by the optical density of the struts. We also measured circulating CD34+ /CD133+ /CD45low cells, and serum levels of stromal cell-derived factor (SDF)-1, interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 at baseline and follow-up. NOD was lower in the EES (0.70 ± 0.06) group than in the BMS (0.76 ± 0.07, P < 0.05) and ZES (0.76 ± 0.06, P < 0.05) groups. The mean neointimal area (R = 0.33, P < 0.05) and mean neointimal thickness (R = 0.37, P < 0.05) were correlated with NOD. Although NOD was not correlated with percent changes in circulating endothelial progenitor cells, and the levels of SDF-1 and IL-8, it was negatively correlated with the change in MMP-9 level (R = - 0.51, P < 0.01). Neointimal maturity might be lower at EES sites than BMS or ZES sites. This might lead to impaired neointimal tissue growth and matrix degradation. These results suggest a specific pathophysiology after DES implantation.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Chemokine CXCL12; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Endothelial Progenitor Cells; Everolimus; Female; Humans; Interleukin-8; Male; Matrix Metalloproteinase 9; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Remodeling

Cytokines, which typically regulate the immune responses, play a role in cardiovascular diseases such as coronary artery diseases (CAD) and ischemic heart diseases (IHD). The aims of this study were to evaluate serum levels of IL-6, IL-8, TGF-β and TNF-α in patients with or without CAD, as well as stable angina, and to assess the effects of drug administration on the serum levels of these cytokines. Serum levels of the cytokines were analyzed in the three groups: patients with acute coronary syndrome, stable angina and participants with normal coronary arteries as controls. Cohort study of the patients showed that Nitrocontin was the only drug used in a significantly different pattern between the groups where it was used less frequently in patients with stable angina compared to the acute coronary syndrome or control groups. Serum levels of the evaluated cytokines were not different neither between the studied groups nor between the groups with variable Gensini scores. However, IL-8 in controls that were not engaged in regular exercise was higher than the controls performing regular exercise. In the stable angina group, TNF-α in non-smokers was higher than the smokers. It was revealed that serum levels of pro-inflammatory cytokines are not associated with atherosclerosis and stable angina in patients from the South-East of Iran. However, suppressed expression of TGF-β, may increase the risk of CAD. Exercise can reduce the risk of CAD through downregulation of pro-inflammatory cytokines.

Topics: Angina, Stable; Case-Control Studies; Coronary Artery Disease; Coronary Vessels; Cross-Sectional Studies; Exercise; Female; Gene Expression; Humans; Interleukin-6; Interleukin-8; Iran; Male; Middle Aged; Nitroglycerin; Risk Factors; Smoking; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vasodilator Agents

Technological developments and enhancement of knowledge level enable heart surgery with low mortality rates in most centers. On the other hand, increased systemic inflammatory response against cardiopulmonary bypass (CPB) plays a critical role in the development of postoperative complications. We aimed to compare the effects of centrifugal pump where it is claimed that blood is exposed to minimal trauma and roller pump techniques on inflammatory response and oxidant status during CPB.. : A total of 40 patients, who had coronary artery disease and underwent coronary artery bypass graft (CABG) surgery using either roller or centrifugal pump between June 2012 and June 2013 were enrolled in this study. Patients over 40 years old and without any known immunologic, infectious, or inflammatory incidents and hematological problems for the past 6 months were included in the study. Two study groups (Group R: roller pump group and Group C: centrifugal pump group) were created. During CABG surgery tumor necrosis factor (TNF) alpha, interleukin (IL)-6, IL-8, superoxide dismutase (SOD), catalase (CAT), and nitric oxide levels were measured before and after CPB.. TNF alpha, IL-6, and IL-8 levels measured before and after CPB were found to be similar between groups. SOD, CAT and Nitric oxide levels were also similar between groups. After the CPB period, glutathione peroxidase enzyme activities in Group R measured after CPB were significantly lower than those measured in Group C. The platelet-activating factor (PAF) levels before CPB usage period were same in both groups, where PAF levels after CPB were found to be significantly higher in roller pump group than centrifugal pump group. At inter-group comparisons, the levels of PAF were same at each group before and after CPB.. The study findings indicate that usage of the centrifugal pump does not have a clear superiority in terms of the effects on inflammatory response and oxidant status during CPB when compared to roller pump. Nevertheless, we believe that our results should be supported by further clinical and experimental studies.

Topics: Adult; Aged; Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Artery Disease; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Oxygen; Postoperative Complications; Superoxide Dismutase; Tumor Necrosis Factor-alpha

We have read with great enthusiasm the article recently published by Boles et al. [...].

Topics: Atherosclerosis; Coronary Artery Disease; Coronary Vessels; Female; Humans; Interferon-gamma; Interleukin-1beta; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Male; Tumor Necrosis Factor-alpha

Eikenella corrodens is a gram-negative bacterium, and although primarily associated with periodontal infections or infective endocarditis, it has been identified in coronary atheromatous plaques. The effect of its lipopolysaccharide (LPS) on human coronary artery endothelial cells (HCAECs) is unknown. Our aim was to examine the mechanism underlying the inflammatory response in HCAECs stimulated with E. corrodens-LPS and to evaluate monocyte adhesion. Endothelial responses were determined by measuring the levels of chemokines and cytokines using flow cytometry. The surface expression of intercellular adhesion molecule 1 (ICAM-1) was determined using a cell-based ELISA, and the adhesion of THP-1 monocytes to HCAECs was also monitored. The involvement of toll-like receptors (TLRs) 2 and 4 was examined using TLR-neutralizing antibodies, and activation of extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) p65 were measured by western blotting and ELISA, respectively. Eikenella corrodens-LPS increased secretion of interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF), and expression of ICAM-1 on the surface of HCAECs, consistent with the increased adhesion of THP-1 cells. Moreover, E. corrodens-LPS interacted with TLR4, a key receptor able to maintain the levels of IL-8, MCP-1, and GM-CSF in HCAECs. Phosphorylation of ERK1/2 and activation of NF-κB p65 were also increased. The results indicate that E. corrodens-LPS activates HCAECs through TLR4, ERK, and NF-κB p65, triggering a pro-atherosclerotic endothelial response and enhancing monocyte adhesion.

Topics: Antibodies, Neutralizing; Cell Adhesion; Cell Survival; Cells, Cultured; Chemokine CCL2; Chemokines; Coronary Artery Disease; Coronary Vessels; Cytokines; Eikenella corrodens; Endothelial Cells; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Lipopolysaccharides; Mitogen-Activated Protein Kinases; Monocytes; NF-kappa B; Phosphorylation; THP-1 Cells; Toll-Like Receptor 2; Toll-Like Receptor 4

The increase in Rheumatoid arthritis (RA) associated mortality is predominantly due to accelerated coronary artery and cerebrovascular atherosclerosis with increased risk of ischemic heart disease about 50% in RA patients compared to controls.. To study the pathogenesis of ischemic heart disease in RA, role of inflammatory cytokine interplay, disease activity and rheumatoid factor positivity.. Eighty RA patients and 44 healthy controls were included. All subjects were younger than 45years for females and 55years for males with exclusion of all traditional risk factors for atherosclerosis. Interleukin (IL) 1, 6 and 18 were assessed in all subjects. RA patients fulfilled ACR/EULAR 2010 criteria and were subjected to Dobutaminestress-echocardiography, diseases activity assessed by DAS-28, X-ray hands for Larsen score and function assessment by HAQ.. RA patients had significantly higher serum IL 1, 6 and 18 than controls (p=0.00 in all). Thirty four (42.5%) patients had hypertensive reaction on Dobutamine-stress-echocardiography, four of them had ischemic change, and 46 (57.5%) had normal reaction. All patients with hypertensive reaction had positive RF (p=0.00), 10 had DAS-28>5.1, 20 had DAS-28 from 3.2 to5.1 and 4 were in remission (p=0.001). CRP was higher in patients with hypertensive reaction (p=0.003) while serum levels of IL1, 6 and 18 showed no significant difference. In all patients, serum levels of IL1, 6 and 18 showed significant positive correlation with VAS, HAQ and DAS-28 (p<0.001 in all). Only IL18 showed significant positive correlation with X-ray score in all patients.. Disease activity and RF positivity play an important risk factor for ischemic heart disease in RA. Serum levels of IL1, 6 and 18 did not help much in detecting patients at risk of ischemic heart disease. Better control of RA disease activity with early remission helps in preventing cardiac complications. More studies on larger number of patients are needed for better understanding of mechanism of ischemic heart disease in RA.

Topics: Adult; Arthritis, Rheumatoid; Atherosclerosis; Coronary Artery Disease; Cross-Sectional Studies; Cytokines; Female; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Risk Factors; Severity of Illness Index

76 patients with coronary heart disease (who had undergone coronary artery bypass grafting) were examined to investigate the role of pro-inflammatory cytokines and enzymes involved in redox regulation, in the mechanisms of development of systemic inflammatory response syndrome. Patients were divided into 2 groups: 1st - patients with coronary heart disease, who as a result of clinical trials has not been set postpericardiotomy syndrome; 2nd - patients with coronary heart disease who have been diagnosed postpericardiotomy syndrome. The blood plasma of both groups indicated intensification of production of interleukin-6, intrleukin-8, as well as - an imbalance in the peroxiredoxin-1 and glutathione peroxidase. These changes by patients with postpericardiotomy syndrome are observed at the earliest time and differed depth of expression. The results of this work confirm the high potential of the investigated indicators for prevention and monitoring postpericardiotomy syndrome development.. Для изучения роли провоспалительных цитокинов и ферментов, участвующих в редокс-регуляции, в механизмах развития системного воспалительного ответа и патогенеза постперикардиотомного синдрома (ПКТС) были обследованы 76 пациентов с ИБС, перенесших аортокоронарное шунтирование. Больные были разделены на две группы: 1-я — больные ИБС, у которых в результате клинических исследований не был установлен ПКТС; 2-я — больные ИБС, у которых был диагностирован ПКТС. В плазме крови у пациентов обеих групп было отмечено усиление продукции IL-6, IL-8, также наблюдали дисбаланс в работе пероксиредоксина-1 и глутатионпероксидазы. У пациентов с ПКТС данные изменения наблюдали в наиболее ранние сроки, они отличались глубиной проявления. Результаты настоящей работы подтверждают высокую эффективность исследованных показателей для предупреждения и мониторинга развития ПКТС.

Topics: Coronary Artery Bypass; Coronary Artery Disease; Glutathione Peroxidase; Humans; Interleukin-6; Interleukin-8; Oxidation-Reduction; Peroxiredoxins; Postpericardiotomy Syndrome; Prospective Studies

Interleukin-8 (IL-8) is a mediator of inflammation and plays an important role in regulating immune responses. To date, several studies have tested the association between IL-8 gene polymorphisms and development of coronary artery disease (CAD), but their results have proved to be inconsistent. We conducted an investigation to assess the relationship between the IL-8 -251A/T (rs4073) sequence variant and CAD in a Chinese population. Between April 2013 and January 2015, 217 patients with coronary angiography-confirmed CAD were enrolled in our study, along with 245 control subjects. IL-8 -251A/T genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism assay. A chi-square test revealed that IL-8 -251A/T genotype distributions significantly differed between CAD patients and control subjects (chi-square = 8.29, P < 0.02). Moreover, multiple-logistic regression analysis showed that individuals carrying TA [odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.01-2.57] and AA (OR = 2.06, 95%CI = 1.21-3.52) genotypes were at increased risk of CAD compared to those with the TT genotype. Under dominant (OR = 1.75, 95%CI = 1.13-2.73) and recessive (OR = 1.54, 95%CI = 1.02-2.37) genetic models, the IL-8 -251A/T polymorphism also significantly correlated with CAD. In conclusion, our results suggest that this variant is an independent risk factor for CAD development under codominant, dominant, and recessive models.

Topics: Asian People; Case-Control Studies; Coronary Artery Disease; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Interleukin-8; Male; Polymorphism, Single Nucleotide

In cells and tissues resistin affects IL-1β, IL-6, IL-8, IL-12 and TNF-α expression, thus suggesting the existence of a multi-cytokine "resistin pathway". We investigated whether such pathway does exist in humans and, if so, if it is associated with cardiovascular risk factors and with major adverse cardiovascular events (MACE). Serum cytokines were measured in 280 healthy subjects from the Gargano Study 2 (GS2) whose BMI, waist circumference, HOMA

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Gene Expression Regulation; Humans; Insulin Resistance; Interleukin-12; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Prospective Studies; Resistin; Risk Factors; Signal Transduction; Triglycerides; Tumor Necrosis Factor-alpha; Waist Circumference

A total of 81 patients with coronary artery disease (CAD) who underwent coronary artery bypass graft (CABG) were enrolled in the study. Patients were divided into 2 groups: Group 1 - without postoperative atrial fibrillation (POAF) (59 patients, 74,6 % men, mean age 65,8±4 years), Group 2 - with early new-onset AF after CABG (22 patients, 90,9 % men, mean age of 67,7±5,4 years). Interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), fibrinogen, superoxide dismutase (SOD), troponin I were studied. During the observation period AF occurred in 27,2 % cases, an average of 4,9±3,8 days after surgery. In the postoperative period were significantly higher in group 2 left atrium (LA) (43,9±3,4 vs. 37,6±3,9 mm, p<0,001), IL-6 (72,7±60,8 vs. 38,0±34,6 pg/ml, p=0,04), IL-8 (11,9±6,0 vs. 7,7±5,4 pg/ml, p=0,01), SOD (2 462,0±2 029,3 vs. 1 515,0±1 292,9 units/g, p=0,04) when compared with group 1. The multivariate analysis showed that the odds ratio for AF development in postoperative period for LA more than 39 mm was 2,1 (95 % CI 1,2-3,8, p=0,0004), IL-6 levels more than 65,18 pg/ml - 1,4 (95 % CI 1,1-2,7, p=0,009), IL-8 levels more than 9,67 pg/ml - 1,2 (95 % CI 1,1-3,7, p=0,009), SOD more than 2948 units/g -1,1 (95 % CI 1,01-2,9, p=0,04). Our study showed that left atrium dimension, high interleukin-6, interleukin-8 and superoxide dismutase levels play an important role in development of atrial fibrillation in early postoperative period after coronary bypass graft surgery.. Обследован 81 пациент с ИБС, последовательно поступивший для проведения операции коронарного шунтирования (КШ). Больные были распределены на две группы: 1-я — 59 пациентов (74,6 % мужчин) без послеоперационной фибрилляции предсердий (ПОФП), средний возраст 65,8±4 года, 2-я — 22 пациента (90,9 % мужчин) с ПОФП, средний возраст 67,7±5,4 года. IL-6, IL-8, IL-10, С-РБ, фибриноген, СОД, количественный тропонин I оценивали при поступлении и после операции на 3,8±1,4 сут. За период наблюдения ПОФП возникла у 27,2 % больных, в среднем на 4,9±3,8 сут после КШ. В послеоперационном периоде достоверно выше во 2 й группе оказался размер левого предсердия (ЛП) — 43,9±3,4 против 37,6±3,9 мм (р<0,001), концентрация IL-6 — 72,7±60,8 против 38,0±34,6 пг/мл (р=0,04), уровень IL-8 — 11,9±6,0 против 7,7±5,4 пг/мл (р=0,01), уровень СОД — 2 462,0±2029,3 против 1515,0±1292,9 ед./г, (р=0,04) при сравнении с 1-й группой. После многофакторного анализа отношение шансов развития ПОФП для ЛП более 39 мм составило 2,1 (95 % ДИ, 1,2–3,8, р=0,0004), для послеоперационного уровня IL-6 более 65,18 пг/мл — 1,4 (95 % ДИ, 1,1–2,7, р=0,009), для послеоперационного уровня IL-8 более 9,67 пг/мл — 1,2 (95 % ДИ, 1,1–3,7, р=0,009), для СОД более 2 948 ед./г — 1,1 (95 % ДИ, 1,01–2,9, р=0,04).Таким образом, значимое влияние на возникновение фибрилляции предсердий в раннем послеоперационном периоде после КШ оказывал размер левого предсердия, повышенная концентрация IL-6, IL-8 и СОД.

Topics: Aged; Atrial Fibrillation; Coronary Artery Bypass; Coronary Artery Disease; Female; Heart Atria; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Organ Size; Postoperative Complications; Prospective Studies; Risk Factors; Russia; Superoxide Dismutase

An altered IL-18 pathway in patients with coronary artery disease has recently been described and this cytokine was shown to be of clinical and prognostic utility. Cardiomyocytes are a target of this cytokine which exerts inflammatory, hypertrophic and profibrotic activities.. The aim of the study was to verify the ability of IL-18 to induce expression of other pro/anti-inflammatory cytokines and to analyse the relationship between these molecules in serum from patients with heart rhythm disorders and coronary artery disease.. All patients in the study were divided into two groups: with heart rhythm disorders and without but with diagnosed coronary artery disease. Heart rhythm disorders included sinus node dysfunction, bradycardia and tachycardia.. The interrelationships among all tested clinical, biochemical and inflammatory parameters with a dependence on median IL-18 values were checked. From all tested parameters only cytokines IL-8, IL-10 and VEGF, were associated with the serum IL-18 levels.. IL-18, IL-8 and VEGF were identified as a factors involved in heart rhythm disorders and coronary artery disease patho-physiology and regarded as markers of prognostic significance and potential therapeutic targets. The demonstration of their in vivo relationship added new insights into the understanding of the interdependence of inflammatory pathways in patients with heart rhythm disorders or coronary artery disease.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Biomarkers; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Interleukin-10; Interleukin-18; Interleukin-8; Male; Middle Aged; Vascular Endothelial Growth Factor A

Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). We studied the safety and feasibility of low-dose rapamycin and its effect on SASP and frailty in elderly undergoing cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median age was 73.9±7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs 4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased. Adipose tissue expression of mRNAs (arbitrary units) for MCP-1 (3585 vs 2020, p=0.06), PPAR-γ (1257 vs 1166), PAI-1 (823 vs 338, p=0.08) increased, whereas interleukin-8 (163 vs 312), TNF-α (75 vs 94) and p16 (129 vs 169) decreased. Cellular senescence-associated beta galactosidase activity (2.2% vs 3.6%, p=0.18) tended to decrease. We observed some correlation between some senescence markers and physical performance but no improvement in frailty with rapamycin was noted. (NCT01649960).

Topics: Adipose Tissue; Aged; Aged, 80 and over; Aging; beta-Galactosidase; Cellular Senescence; Chemokine CCL2; Coronary Artery Disease; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p21; Female; Frail Elderly; Gait; Humans; Immunosuppressive Agents; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 3; Percutaneous Coronary Intervention; Phenotype; Pilot Projects; Plasminogen Activator Inhibitor 1; PPAR gamma; RNA, Messenger; Sirolimus; Treatment Outcome; Tumor Necrosis Factor-alpha; Walk Test

Coronary artery disease (CAD) and hypertension are the main reasons of ischemic heart diseases (IHDs). Cytokines as the small glycoproteins are the main arm of immune system and manipulate all of the cardiovascular diseases. The aim of the current study was to examine the effects of treatment of hypertension and CAD on serum levels of IL-6, IL-8, TGF-β and TNF-α.. This interventional study was performed on the patients with hypertension without CAD (group 1), hypertension and CAD (group 2), CAD but not hypertension (group 3) and without hypertension and CAD as controls (group 4). The patients received routine treatment for hypertension and CAD. Serum levels of IL-6, IL-8, TGF-β and TNF-α were analyzed in the groups treated with various drugs, using ELISA technique.. With regard to the medications, Atorvastatin, Losartan and Captopril were administered more in patients (groups 1, 2 and 3) than the patients without hypertension and CAD. The results revealed that serum levels of TGF-β and IL-6 were significantly increased and decreased, respectively, in the groups 1, 2 and 3 when compared to group 4. Serum levels of TGF-β were also increased in females in comparison to males in the group 4.. According to the results it seems that Atorvastatin, Losartan and Captopril have reduced inflammation in in vivo conditions via downregulation of IL-6 and upregulation of TGF-β.

Topics: Antihypertensive Agents; Atorvastatin; Captopril; Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Inflammation; Interleukin-6; Interleukin-8; Iran; Losartan; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Up-Regulation

Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD). Enhanced vascular inflammation is implicated as a pathophysiologic mechanism but obesity is confounding. We aimed to address the association of OSA with inflammatory biomarkers in a nonobese cohort of revascularized patients with CAD and preserved left ventricular ejection fraction.. Cross-sectional analysis of baseline investigations of a randomized controlled trial.. Clinic-based.. There were 303 nonobese patients with CAD, of whom 213 with OSA (apnea-hypopnea index [AHI] ≥15 events/h) and 90 without OSA (AHI < 5 events/h). Obese patients with CAD and OSA (N = 105) were chosen as an additional control group.. None.. Circulating levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α were assessed in relation to OSA diagnosis based on AHI ≥ 15 events/h as well as oxygen desaturation index (ODI) ≥ 5 events/h.. Nonobese patients with OSA had significantly higher levels of hs-CRP and IL-6 than those without OSA. The values did not differ significantly between obese and nonobese patients with OSA. In bivariate regression analysis, AHI ≥ 15 events/h was associated with all four biomarkers but not so in the multivariate model after adjustment for confounders. ODI ≥ 5 events/h was associated with hs-CRP (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.13-1.99) and IL-6 (OR 1.30; 95% CI 1.05-1.60) in multivariate analysis.. OSA with ODI ≥ 5 was independently associated with increased inflammatory activity in this nonobese CAD cohort. The intermittent hypoxemia, rather than the number of apneas and hypopneas, appears to be primarily associated with enhanced inflammation.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Odds Ratio; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Vascular disease is promoted by systemic inflammation that can arise from sites distal to the affected vessels. We sought to characterize the net inflammatory potential of serum from patients with coronary artery disease (CAD) using cultured endothelial cells as a cumulative biosensor.. Serum samples from CAD patients (N = 45) and healthy control subjects (N = 48) were incubated with primary human coronary artery endothelial cells at a 1:10 dilution for 4 h, followed by isolation of the cellular RNA. Alteration of inflammation-responsive elements (adhesion molecules and cytokines) was assessed by gene expression. Specific indicators included intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and interleukin-8 (IL-8). Additionally, the cytokine levels in serum samples from all subjects were quantified. Serum from CAD subjects induced greater endothelial ICAM-1, VCAM-1, and IL-8 expression compared to healthy control serum (p < 0.001 for each analysis). The three indicators of inflammatory potential (ICAM-1, VCAM-1, and IL-8 mRNA) trended independently of each other and also of serum inflammatory biomarkers. IL-8 expression correlated negatively with serum HDL levels but positively correlated with VLDL, plasminogen activator inhibitor-1 and C-reactive protein. Interestingly, serum levels of cytokines in CAD patients were not statistically different from healthy control subjects. A year of follow-up in a sub-group of CAD subjects revealed relatively stable measures.. As yet unidentified circulating factors in the serum of CAD patients appear to activate endothelial cells, leading to upregulation of adhesion molecules and chemokines. This cumulative assay performed well in terms of discriminating patients with CAD compared to healthy subjects, with greater range and specificity than specific inflammatory markers.

Topics: Adolescent; Adult; Age Factors; Aged; Biological Assay; Biosensing Techniques; Body Mass Index; Case-Control Studies; Cohort Studies; Coronary Artery Disease; Coronary Vessels; Demography; Endothelial Cells; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Linear Models; Luminescent Measurements; Male; Middle Aged; Myocardial Infarction; Sex Characteristics; Time Factors; Vascular Cell Adhesion Molecule-1; Young Adult

To investigate the long-term prognostic significance of baseline plasma IL-8 levels in a group of well-characterized male patients presenting with acute coronary syndrome.. IL-8 is a cytokine that has been implicated in the pathogenesis of atherosclerosis and acute coronary syndrome. Elevated plasma levels have been reported in patients with acute coronary syndrome.. Baseline plasma IL-8 levels were measured in 180 male patients with acute coronary syndrome who were referred for coronary angiography and followed prospectively for the development of all-cause mortality for 5 years.. In a multivariate model that included a wide variety of baseline clinical, laboratory and angiographic parameters in the selection process, baseline plasma IL-8 levels (analyzed as a continuous variable) emerged as a significant predictor of all-cause mortality at 5 years (HR, 1.43; 95% CI, 1.08-1.88; p = 0.0123). Furthermore, in 3 additional multivariate models that also included in the selection process a number of contemporary biomarkers with established prognostic efficacy in ACS (i.e., NT-proBNP, hs-CRP, hemoglobin and RDW), IL-8 remained an independent predictor of all-cause mortality at 5 years.. Elevated baseline plasma levels of IL-8 are associated with an increased risk of long-term all-cause mortality in patients with acute coronary syndrome. Furthermore, this association is independent of a variety of clinical, laboratory and angiographic variables, including contemporary biomarkers with established prognostic efficacy in acute coronary syndrome.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Atherosclerosis; Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Artery Disease; Erythrocytes; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Hemoglobins; Humans; Interleukin-8; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Renal Insufficiency

We conducted a case-control study to investigate the genetic variants Interleukin-1β(IL-1β) +3953 C/T (rs1143634), IL-6 -174G/C (rs1800795), IL-8 -251T/A (rs4073), and IL-10 -1082A/G (rs1800896) and -819C/T (rs1800871) in the development of coronary artery disease (CAD). A total of 410 individuals with CAD were enrolled between January 2012 and December 2014. Genotyping of the five gene polymorphisms was performed using the polymerase chain reaction combined with restriction fragment length polymorphism methodology. By multivariate logistic regression analysis, we found that the frequencies of the CC genotype and the C allele of IL-6 -174G/C were significantly correlated with a higher risk of CAD; the adjusted ORs (95%CIs) were 2.37 (1.37-4.14) and 1.49 (1.19-1.86), respectively. In addition, the AG and GG genotypes and the G allele of IL-10 -1082A/G were also significantly associated with a higher risk of CAD, and the ORs (95%CIs) were 1.42 (1.04-1.95), 2.16 (1.42-3.30), and 1.56 (1.27-1.93), respectively. However, IL-1β+3953 C/T, IL-8 -251T/A, and IL-10 -819C/T did not significantly correlate with CAD risk. Our study suggests that the IL-6 -174G/C (rs1800795) and IL-10 -1082A/G (rs1800896) polymorphisms might be involved in the pathogenesis of CAD, and likely contribute to the genetic susceptibility for CAD.

Topics: Adult; Aged; Aged, 80 and over; Alleles; Case-Control Studies; Coronary Artery Disease; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Humans; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Risk Factors

Leukotrienes are important lipid inflammatory mediators that play a pivotal role in the pathogenesis of atherosclerosis. We aimed to construct a network of interactions between leukotrienes and inflammatory biomarkers and evaluate the expression of key members of the leukotriene pathway and leukotriene-induced inflammatory molecules in patients with coronary artery disease (CAD) and healthy controls.. Leukotrienes and their regulatory inflammatory molecules reported in the literature were used to construct a biological network employing Gene spring GX v12.5. Key leukotriene genes and their closely interacting members were selected for expression study in 64 patients and 64 matched controls. Four single nucleotide polymorphisms(SNPs) (rs6538697, rs2660898, rs17525495 and rs1978331) in the leukotriene A4 hydrolase(LTA4H) gene were genotyped using SYBR green method, and plasma leukotriene B4 (LTB4) levels were measured using ELISA.. The expression levels of arachidonate 5-lipoxygenase(ALOX5), LTA4H, tumor necrosis factor (TNF) and interleukin-8 (IL-8) genes were significantly higher in patients than in the controls(p＜0.05). IL-8(r=0.35-0.47) and TNF (r=0.42-0.53) expression levels exhibited strong correlations with the leukotriene genes. The SNPs rs17525495 and rs1978331 were associated with LTA4H mRNA expression, while LTA4H and IL-8 levels were associated with CAD. The addition of these two markers to the conventional risk factors improved the c-statistics(area under the receiver operating characteristic(ROC) curve) from 0.75 to 0.93(p＜0.01), with a Net Reclassification Index of 0.45(p＜0.01) and Integrated Discrimination Improvement of 0.26(p＜0.01).. Leukotrienes and inflammatory genes, in particular, LTA4H and IL-8, exhibit close association in subjects with cardiovascular disease. Assessing these markers may provide incremental value for predicting cardiovascular risk beyond that obtained with classical risk factors.

Topics: Aged; Algorithms; Arachidonate 5-Lipoxygenase; Case-Control Studies; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Epoxide Hydrolases; Female; Gene Expression Profiling; Genotype; Humans; Inflammation; Interleukin-8; Leukotrienes; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; Tumor Necrosis Factor-alpha

Interleukin 8 (IL8) has been contradictorily associated with the risk of myocardial infarction (MI).. To investigate the association of IL8 serum levels with the risk of MI and the association of the IL8 (IL8) and IL8 receptors (CXCR1 and CXCR2) genetic variants with IL8 levels and MI risk in a large case control study, the Stockholm Heart Epidemiology Program.. IL8 levels (pg/mL) were divided into quartiles and the MI risk was calculated by logistic regression and expressed as odds ratio (OR) and 95% CI. Two IL8 SNPs (rs4073A/T, rs2227306C/T) and three SNPs tagging CXCR1 and CXCR2 (rs4674258C/T, rs1008563C/T, rs6723449T/C) were analyzed for association with IL8 levels and with MI risk. Multivariate adjusted ORs for MI risk by IL8 levels in the highest quartiles indicated reduced point estimates in both women (OR 0.37; 95% CI 0.2-0.8) and men when compared to the lowest quartile. In female cases, IL8 levels decreased progressively in the six months after MI (p=0.03). IL8, CXCR1 and CXCR2 genetic variants were not associated with IL8 levels. In men, the T allele at the IL8 SNP rs4073 was associated with a slight increase in the MI risk under an additive and a recessive model of inheritance.. IL8 serum levels were associated with a reduced occurrence of MI among women, whereas IL8 was associated with a slightly increased risk among men, possibly through different mechanisms. These data suggest that the biological effects of IL8 on MI risk may vary over time and warrant further cohort studies with repetitive IL8 measurements.

Topics: Aged; Case-Control Studies; Coronary Artery Disease; Female; Genetic Predisposition to Disease; HapMap Project; Humans; Interleukin-8; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Polymorphism, Single Nucleotide; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Risk Factors; Sweden

Left main coronary artery disease (LMCAD) is a particular severe phenotype of coronary artery disease (CAD) and heritability. Interleukin (IL) may play important roles in the pathogenesis of CAD. Although several single nucleotide polymorphisms (SNPs) identified in IL related genes have been evaluated for their roles in inflammatory diseases and CAD predisposition, the investigations between genetic variants and CAD phenotype are limited. We hypothesized that some of these gene SNPs may contribute to LMCAD phenotype susceptibility compared with more peripheral coronary artery disease (MPCAD). In a hospital-based case-only study, we studied IL-1A rs1800587 C/T, IL-1B rs16944 G/A, IL-6 rs1800796 C/G, IL-6R rs7529229 T/C, IL-8 rs4073 T/A, IL-10 rs1800872 A/C, and IL-10 rs1800896 A/G SNPs in 402 LMCAD patients and 804 MPCAD patients in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and ligation detection reaction (LDR) method. When the IL-6R rs7529229 TT homozygote genotype was used as the reference group, the CC or TC/CC genotypes were associated with the increased risk for LMCAD (CC vs. TT, adjusted odds ratio(OR)=1.46, 95% confidence interval (CI)=1.02-2.11, p=0.042; CC+TC vs. TT, adjusted OR=1.31, 95% CI=1.02-1.69, p=0.037). None of the other six SNPs achieved any significant differences between LMCAD and MPCAD. The present study suggests that IL-6R rs7529229 T/C functional SNP may contribute to the risk of LMCAD in a Chinese population. However, our results were limited. Validation by a larger study from a more diverse ethnic population is needed.

Topics: China; Coronary Artery Disease; Coronary Vessels; Gene Frequency; Genetic Predisposition to Disease; Humans; Interleukin-10; Interleukin-1alpha; Interleukin-1beta; Interleukin-6; Interleukin-8; Polymorphism, Single Nucleotide; Receptors, Interleukin-6; Risk Factors; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

In recent years, the scientific publications about disorder the scientific publications appeared concerning derangement of content of alpha-defensins in neutrophils of patients with atherosclerosis. The interest increases both to different derangement of protein-synthesizing function of neutrophils and to biological effects caused by defensins and other peptides and proteins taking part in anti-microbial defense of human organism. With purpose to study content of alpha-defensins (1-3) and synthesis and liberation of other proteins and peptides by neutrophils the concentrations of alpha-defensins, lipoprotein (alpha), C-reactive protein, precursor of cerebral natriuretic peptide, coagulation factor VII and von Willebrand factor were determined in supernatants of leukocytal cultures in patients with exertional angina pectoris and atherosclerosis of lower extremities. The evaluation of loading test was implemented in vitro with alpha-tumor necrosis factor in vitro. Simultaneously, serum concentrations of cytokines and pro-atherogenic proteins were analyzed. It is established that in patients with ischemic heart disease derangement of protein-synthesizing function of neutrophils is observed. The derangement is manifested in the form of decrease of synthesis of alpha-defensins, increase of synthesis of lipoprotein (alpha), precursor of cerebral natriuretic peptide, C-reactive protein and von Willebrand factor. The pathogenic role of alpha-tumor necrosis factor is established. The increase of concentration of interleukin-8 in blood serum is revealed.

Topics: Adult; Aged; alpha-Defensins; Angina Pectoris; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Factor VII; Female; Humans; Interleukin-8; Leukocytes; Lipoproteins, HDL; Male; Middle Aged; Neutrophils; Peripheral Arterial Disease; Tumor Necrosis Factor-alpha; von Willebrand Factor

Cardiovascular diseases are the leading cause of morbidity and mortality. In spite of improved pharmacological interventions, the clinical outcome or response to therapy is poorly linked with the reversal of signs and symptoms of the disease.. Keeping this in view, we evaluated the post-treatment effect of standard therapies on traditional risk factors as well as inflammatory markers in 116 non-diabetic subjects with stable CAD undergoing treatment with conventional drugs for >3 months (Group-II) and 50 normal healthy controls (Group-I). We employed a top-down approach through Microarray and bioinformatics analysis to evaluate the distinct molecular signatures that remain unresponsive to the current therapies employed in clinics. Despite potent effects of therapy on serum cholesterol and LDL-C, triglycerides, VLDL-C and inflammatory markers such as hsCRP, Ox-LDL, IL-18, TNF-α and IL-6 remained high in these subjects versus controls. Microarray analysis revealed that despite treatment 513 genes were differentially expressed that play important role in various biological processes such as, i.e. inflammation (CXCR4, CXCL2, PTGS2), immune imbalance (IL-8, IL-Iß, CCL3), and active atherosclerosis (DUSP-1, OSM, ATF3). A positive correlation between hsCRP, IL-18, IL-8, PTGS2 and IL-Iß genes points these as candidate genes and therapeutic targets.. Our results clearly demonstrate that standard therapies for treatment and prevention of CAD fail to protect these subjects from ongoing inflammation and immune imbalance. Using a systems-based approach we propose a list of "Core-Genes" as probable candidate genes for therapeutic targeting.

Topics: Adult; Aged; Chemokines, CXC; Computational Biology; Coronary Artery Disease; Cyclooxygenase 2; Dual Specificity Phosphatase 1; Female; Gene Expression Profiling; Humans; Inflammation; Interleukin-8; Lipids; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Oncostatin M; Risk Factors; ROC Curve; Systems Theory

We aimed to investigate the effects of off-pump coronary artery bypass grafting, pulsatile cardiopulmonary bypass, and non-pulsatile cardiopulmonary bypass techniques on the inflammatory response and the central nervous system in the current study.. A total of 32 patients who were scheduled for elective coronary artery bypass graft surgery were included in the study. The patients were allocated into three different groups according to the perfusion techniques used during the cardiopulmonary bypass procedure as follows: off-pump coronary artery bypass grafting group (n=10); pulsatile cardiopulmonary bypass group (n=11); and non-pulsatile cardiopulmonary bypass group (n=11). Serum interleukin-6, interleukin-8, tumor necrosis factor-alpha and S-100beta levels were measured preoperatively, and at 0, 6, and 24 hours postoperatively.. The postoperative increase in the levels of interleukin-6 and interleukin-8 was significantly lower in the off-pump group compared to the other two groups (p<0.05), while there was no significant difference in tumor necrosis factor-alpha levels between the groups. Postoperative S-100β levels, an indicator of cerebral injury, was significantly lower in the off-pump CABG group compared to the other two groups (p<0.05).. We found that off-pump coronary artery bypass grafting had less negative effects on inflammatory response and central nervous system compared to pulsatile cardiopulmonary bypass and non-pulsatile cardiopulmonary bypass techniques.

Topics: Aged; Cardiopulmonary Bypass; Coronary Artery Disease; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Nerve Growth Factors; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Time Factors; Tumor Necrosis Factor-alpha

Inflammatory biomarkers and chemoattractants characteristic and important for different types (lipid; inflammatory erosive; degenerative necrotic) of unstable plaques in coronary arteries were identified and studied in male patients with coronary atherosclerosis without acute coronary syndrome we studied. Among the three types of unstable plaques, elevated concentrations of IL-1β, IL-6, IL-8, IL-18 and monocyte chemotactic protein-1 were characteristic of not only inflammatory erosive type, but also lipid type compared with degenerative necrotic type. Thus, intensification of the inflammatory process plays an important role in the development of not only inflammatory and destructive, but also of lipid type of unstable atherosclerotic plaques.

Topics: Chemokine CCL2; Coronary Artery Disease; Coronary Vessels; Humans; Inflammation; Interleukin-18; Interleukin-1beta; Interleukin-6; Interleukin-8; Interleukins; Lipids; Male; Plaque, Atherosclerotic

To test whether ETS-related gene (Erg) inhibits tumor necrosis factor (TNF)-α-dependent endothelial activation and inflammation.. Endothelial activation underlies many vascular diseases, including atherosclerosis. Endothelial activation by proinflammatory cytokines decreases expression of the ETS transcription factor Erg. By using human umbilical vein endothelial cells (HUVECs), we showed that Erg overexpression by adenovirus (AdErg) repressed basal and TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), and interleukin 8 (IL-8). Erg inhibited TNF-α-dependent activation of the ICAM-1 promoter, nuclear factor (NF)-κB activity, and NF-κB p65 phosphorylation. Basal NF-κB activity was also inhibited by Erg overexpression. Chromatin immunoprecipitation showed that Erg binds to the ICAM-1 proximal promoter region, which contains 7 putative ETS binding sites. To test the anti-inflammatory role of Erg in vivo, we used a murine model of TNF-α-dependent acute inflammation. The injection of AdErg into the paw decreased TNF-α-induced inflammation compared with control. Finally, staining of human coronary plaques showed loss of Erg expression from the endothelium overlaying active plaque shoulders.. We have identified a novel physiological anti-inflammatory pathway under the control of the transcription factor Erg; this pathway inhibits NF-κB-dependent transcription and TNF-α-induced inflammation in vivo. These results suggest a novel approach to anti-inflammatory therapies.

Topics: Animals; Base Sequence; Binding Sites; Cells, Cultured; Coronary Artery Disease; Disease Models, Animal; Down-Regulation; Endothelial Cells; Humans; Inflammation; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-8; Mice; Mice, Inbred C57BL; Molecular Sequence Data; NF-kappa B; Phosphorylation; Promoter Regions, Genetic; RNA Interference; Time Factors; Trans-Activators; Transcription Factor RelA; Transcriptional Regulator ERG; Transfection; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Chlamydia pneumoniae heat shock protein (cHSP) 60 is produced during chronic chlamydial infection and activate innate immune and inflammatory responses thereby contributing to atherogenesis. However, to date there is no apparent signaling cascade delineated in human atherosclerotic plaques in C. pneumoniae positive coronary artery disease (CAD) patients. Atherosclerotic plaques were obtained from 40 CAD patients (28 men, 12 women) attending Department of Cardio Thoracic and Vascular Surgery Safdarjung Hospital, New Delhi. Atherosclerotic plaques were used for gene expression studies at RNA level by real-time PCR and to study expression of ERK1/2, JNK1/2, NF-kB, IkkB and MCP-1 at protein level by immunoblotting. Significantly higher (p < 0.001) RNA expression was found for IL-8, TLR-2/4, TGF-β, ICAM1, VCAM1 and MAPKinase genes, whereas significantly lower (p < 0.001) RNA expression for SMAD4, IkkB, BRCA1 and IL-10 was detected in cHSP60-positive atheromatous plaque of CAD patients. Moreover, at proteins level pERK1/2 (p = 0.05), NF-kB (p = 0.017), MCP-1 (p = 0.011) was higher and IkkB expression was lower (p = 0.038) in cHSP60-positive atheromatous plaque of CAD patients. This study by using human atheromatous plaques at RNA and protein levels demonstrated higher expression of TLR-2/4, IL-8, ICAM1, VCAM1, ERK1/2 and NF-kB in cHSP60-positive CAD patients.

Topics: Adult; Chaperonin 60; Chemokine CCL2; Chlamydia Infections; Coronary Artery Disease; Extracellular Signal-Regulated MAP Kinases; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Interleukin-8; Male; MAP Kinase Kinase 4; Middle Aged; NF-kappa B; Plaque, Atherosclerotic; Signal Transduction; Toll-Like Receptor 4

Atherosclerosis is a progressive disease characterized by a series of inflammatory responses in the large and medium arteries. Th17 cells, a distinct T cell lineage which has recently been identified, have a proinflammatory role and are implicated in many inflammatory conditions in humans and mice. The present study was designed to assess whether Th17 cells are associated with human coronary atherosclerosis.. Flow cytometry was used to examine Th17 cell frequencies in patients with coronary atherosclerosis and in healthy individuals. ELISA and real-time RT-PCR were performed to investigate circulating interleukin (IL)-17 (the signature cytokine of Th17 cells) and IL-8 (the cytokine induced by IL-17) protein and mRNA levels.. Significantly increased Th17 cell frequencies are observed in patients with coronary artery disease compared to healthy controls. The protein and mRNA levels of IL-17 and IL-8 are also significantly elevated in patients with atherosclerosis compared to healthy volunteers. Furthermore, mRNA levels of IL-17 and IL-8 are correlated with each other and with peripheral neutrophil counts.. Our findings indicate that Th17 cells and their signature cytokine are involved in the process of atherogenesis. These data suggest that Th17 cells link T cell activity with neutrophilic inflammation in atherosclerosis.

Topics: Adult; Atherosclerosis; Case-Control Studies; Cell Count; Coronary Artery Disease; Female; Humans; Inflammation; Interleukin-17; Interleukin-8; Male; Middle Aged; Neutrophils; RNA, Messenger; Th17 Cells

The innate immune response elicited by activation of TLRs (Toll-like receptors) plays an important role in the pathogenesis of atherosclerosis. We hypothesized that cardiovascular risk factors are associated with the activation status of the innate immune system. We therefore assessed the responsiveness of TLRs on circulating cells in two groups of patients with established atherosclerosis and related this to the presence of cardiovascular risk factors. TNF (tumour necrosis factor)-α release induced by TLR2 and TLR4 activation was measured in patients with established coronary [PCI (percutaneous coronary intervention) study, n=78] or carotid artery disease [CEA (carotid endarterectomy) study, n=104], by stimulating whole blood samples with lipopolysaccharide (TLR4 ligand) and Pam3CSK4 [tripalmitoylcysteinylseryl-(lysyl)4; TLR2 ligand]. As an early activation marker, CD11b expression was measured by flow cytometry on CD14+ cells. Obesity was the 'only' risk factor that correlated with the TLR response. In both studies, obese patients had significantly higher TNF-α levels after stimulation of TLR2 compared with non-obese patients [16.9 (7.7-49.4) compared with 7.5 (1.5-19.2) pg/ml (P=0.008) in coronary artery disease and 14.6 (8.1-28.4) compared with 9.5 (6.1-15.7) pg/ml (P=0.015) in carotid artery disease; values are medians (interquartile range)]. Similar results were obtained following TLR4 stimulation. The enhanced inflammatory state in obese patients was also confirmed by a significant increased expression of the activation marker CD11b on circulating monocytes. In conclusion, obesity is associated with an enhanced TLR response in patients suffering from established atherosclerotic disease.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Atherosclerosis; Carotid Artery Diseases; CD11b Antigen; Cohort Studies; Coronary Artery Disease; Endarterectomy, Carotid; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Risk Factors; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

As accumulation of monocytes and macrophages is a feature of atherosclerotic plaque at all stages, inflammatory gene expression profiling of peripheral blood mononuclear cells may provide a more reliable measure of atherogenesis than systemic inflammatory markers. The aim of this study was to determine whether expression patterns of inflammatory regulators in blood are correlated with severity and progression of coronary artery disease.. PCR expression arrays were used to profile mRNA levels of 84 candidate genes in blood from three patients with persistent perfusion defects, three with improved perfusion, and two without perfusion defects as measured by serial PET myocardial perfusion imaging. A case-control study compared expression of inflammatory genes in 25 patients with stress-induced perfusion defects and 25 controls using quantitative real-time PCR.. Expression array analysis identified IL-8, CXCR1, and CXCR2 as genes showing increased expression in patients with persistent perfusion defects. The case-control study confirmed a significant increase in CXCR1 (P=0.04) and CXCR2 (P=0.002) mRNAs in blood in males with obstructive CAD, but not in females. There was no difference in IL-8 mRNA level between cases and controls (P=0.1). Coordinated expression of CXCR1 and CXCR2 mRNA was more pronounced in controls (r=0.96) than in patients with perfusion defects (r=0.73).. mRNA levels for CXCR1 and CXCR2 are increased in blood in males with obstructive CAD and decreased in patients with improved perfusion, suggesting that these genes may serve as markers of disease severity and progression.

Topics: Aged; Analysis of Variance; Biomarkers; Case-Control Studies; Coronary Artery Disease; Coronary Circulation; Disease Progression; Gene Expression Profiling; Genetic Association Studies; Humans; Inflammation Mediators; Interleukin-8; Male; Middle Aged; Myocardial Perfusion Imaging; Oligonucleotide Array Sequence Analysis; Positron-Emission Tomography; Real-Time Polymerase Chain Reaction; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Severity of Illness Index; Sex Factors; Up-Regulation

To observe the monocytic expression of CD(40) and plasma IL-8 concentration in senile CHD (coronary heart disease) patients with depressive disorder and examine the effects of immunological factors in depressive disorder and CHD.. A total of 100 senile CHD patients (> 60 yr old) were divided into 3 group: control group (A, n = 30), depression score ≤ 20 & anxiety score ≤ 6; therapy group (B, n = 35), depression score ≥ 30 & anxiety score ≤ 6, psychological evaluations with HAMD (Hamilton depression rating scale) from Day 1 pre-operation to Day 7 post-operation; non-therapy group (C, n = 35), depression score ≥ 30 & anxiety score ≤ 6. They underwent the same operation: lumbar decompression & fusion, stripping of great saphenous vein and repair of indirect hernia. At Day 1 pre-operation and Day 7 post-operation, 2 ml venous blood was drawn for the detection of monocytic expression of CD(40) and plasma concentration of IL-8 (interleukin-8).. Depressive value of Group B at post-operation was lower than that at pre-operation and Group C ((25.1 ± 2.9) vs (33.2 ± 1.4) & (34.2 ± 0.8), P < 0.05); the pre-operative expression of CD(40) of Group A was lower than the other groups ((123 ± 18) vs (197 ± 23) & (204 ± 26), P < 0.05). And Group B at post-operation was lower than Group C ((147 ± 19) vs (212 ± 18), P < 0.05); the pre-operative concentration of IL-8 was lowest in Group A ((85 ± 16) ng/L vs (151 ± 18) ng/L & (164 ± 22) ng/L, P < 0.05). And Group B at post-operation was lower than Group C ((158 ± 19) ng/L vs (197 ± 24) ng/L, P < 0.05). There were significantly positive correlations between depression scores, the expression of CD(40) and the plasma concentration of IL-8.. Depressive disorders elevate the monocytic expression of CD(40) and raise the plasma concentration of IL-8 in senile CHD patients. Some immunological factors may play a important role in depressive disorder and CHD.

Topics: Coronary Artery Disease; Depressive Disorder; Humans; Interleukin-8

Interleukin-8 is a strong mediator of inflammation and has been implicated in the biochemical pathways involved in a wide range of inflammatory diseases including atherosclerosis. We investigated the potential influence of two common functional polymorphisms of the interleukin (IL)-8 gene: -251A/T and 781C/T on susceptibility to in stent restenosis (ISR) following percutaneous coronary intervention (PCI). The hypothesis was tested by screening for the prevalence of the above polymorphisms in 201 coronary artery disease (CAD) patients subjected to PCI and presenting with symptoms or signs of recurrent ischemia. Patients were angiographically re-evaluated and formed the ISR group (n = 73) and the non-ISR group (n = 128) based on the presence or absence of ISR. One hundred and forty-seven subjects without angiographic evidence of CAD formed a reference control group (non-CAD group). A borderline statistically significant higher frequency of the TT(251)TT(781) combined genotype was observed in patients with ISR on re-evaluation compared with patients with normal follow-up angiography. The predominance of TT(251)TT(781) was independent of conventional risk factors for cardiovascular disease. Consequently, T(251)T(781) haplotype was significantly more common in the ISR group. The above observations indicate that the genetic diversity of the IL-8 gene influences patient susceptibility to ISR and suggests the implication of IL-8-mediated pathways in the process of ISR. However, the rarity of T(251)T(781) haplotype makes any clinical application of the above observations unfeasible.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Female; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-8; Male; Middle Aged; Phenotype; Polymorphism, Genetic; Postoperative Complications

Malnutrition, inflammation, and renal osteodystrophy parameters with resultant coronary calcification (CC) are associated with increased cardiovascular mortality in adults. Previous pediatric studies demonstrated CC in children but none assessed for an association between inflammation, malnutrition, renal osteodystrophy, and CC. To assess CC, ultrafast computerized tomogram was obtained for 16 pediatric patients (6 females; median age 17.2 years; range 9.1-21.2 years) receiving hemodialysis for >/=2 months. Inflammation was assessed by serum IL-6, IL-8, and C-reactive protein levels on the day of the computerized tomogram scan; nutrition parameters included serum albumin, cholesterol, the body mass index standard deviation score, and normalized protein catabolic rate. Renal osteodystrophy parameters included time-averaged serum calcium, phosphorus, total PTH, and calcitriol/calcium dose. Patients received hemodialysis thrice-weekly; mean single pool Kt/V 1.48+/-0.13; and mean normalized protein catabolic rate 1.27+/-0.17 g/kg/day. Five of 16 patients had CC. Patients with CC were older (19.1+/-2.1 vs. 15.4+/-3.1 months; P=0.03), had longer dialysis vintage (49.4+/-15.3 vs. 17.2+/-10.5 months, P=0.0002), lower serum cholesterol (122+/-17.7 vs. 160.4+/-10.6 mg/dL, P=0.02), and higher phosphorus (9.05+/-1.2 vs. 6.1+/-0.96 mg/dL, P=0.0001). Mean serum albumin and normalized protein catabolic rate did not differ for patients with CC. All patients had elevated IL-6 and IL-8 levels compared with healthy norms; the mean IL-6, IL-8, and C-reactive protein levels were not different in patients with CC. Coronary calcification was prevalent in older children receiving maintenance hemodialysis with a longer dialysis vintage. Worse renal osteodystrophy control and malnutrition (low cholesterol) may contribute to CC development.

Topics: Adolescent; C-Reactive Protein; Calcinosis; Child; Child Nutrition Disorders; Cholesterol; Chronic Kidney Disease-Mineral and Bone Disorder; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Malnutrition; Nutritional Status; Renal Dialysis; Serum Albumin; Young Adult

Raised levels of inflammation markers are associated with worse prognosis in patients with coronary artery disease. It is generally believed, although it has never been proven, that inflammation markers are released from (un)stable plaques in coronary arteries. We investigated this issue by directly comparing levels of inflammation markers in coronary and systemic blood.. Patients with acute coronary syndrome (N = 11), stable angina pectoris (N = 10) and controls with noncoronary origin of chest pain (N = 9) were included in the study. Intracoronary blood samples were taken at the culprit lesion in the coronary artery in patients with acute coronary syndrome and from any coronary artery in the other two groups, together with systemic blood samples from the femoral vein and artery. Levels of high-sensitivity C reactive protein (hsCRP), interleukin 6, interleukin 8, interleukin 10, soluble receptor for interleukin 2 (tR IL-2) and myeloperoxidase were measured in all samples.. We found significantly elevated levels of hsCRP and interleukin 10 in patients with acute coronary syndrome compared with patients with stable angina and the control patients. Notably, we did not find any difference between intracoronary and systemic levels of any inflammatory marker in patients with acute coronary syndrome. Furthermore, no difference between intracoronary and systemic levels of markers was present in patients with stable angina or in the control group.. We observed that excess circulating inflammation markers, being characteristic of unstable coronary artery disease, are released from noncoronary sources. Thus, it may be speculated that systemic inflammation precedes local inflammation at the plaques, thereby transforming coronary disease from a stable to an unstable form.

Topics: Acute Coronary Syndrome; Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; C-Reactive Protein; Cardiac Catheterization; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Female; Humans; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Peroxidase; Prognosis; Receptors, Interleukin-2; Reference Values

Endothelial progenitor cells (EPC) may participate in the repair of injured coronary endothelium. We have recently identified EPC co-expressing the osteoblastic marker osteocalcin [OCN (+) EPC] and found that their numbers are increased in patients with early and late coronary atherosclerosis. The current study was designed to test the hypothesis that early coronary atherosclerosis is associated with the retention of osteogenic EPC within the coronary circulation.. Blood samples were taken simultaneously from the proximal aorta and the coronary sinus from 31 patients undergoing invasive coronary endothelial function testing. Using flow cytometry, peripheral blood mononuclear cells were analysed for EPC markers (CD133, CD34, KDR) and OCN. The net gradient of EPC was calculated by multiplying the coronary blood flow by the arteriovenous EPC gradient (a negative net gradient indicating retention of EPC). Similarly, serum samples were analysed for stromal cell-derived factor-1 alpha (SDF-1 alpha) and interleukin-8 (IL-8) and their net production calculated. Compared with controls (n = 17) patients with endothelial dysfunction (ED, n = 14) had a significant net retention of CD34+/CD133-/KDR+/OCN+ EPC [118.38 (0.00, 267.04) vs. -112.03 (838.36, 0.00), P = 0.004]. The retention of OCN (+) EPC correlated with the degree of ED. Patients with ED also showed a net retention of CD34+/CD133-/KDR+ EPC (P = 0.010). Net production of IL-8 was positive in ED [1540.80 (-300.40, 21744.10)pg/mL] but negative in controls [-3428.50 (-11225.00, 647.48), P = 0.025].. Our study demonstrates that patients with early coronary atherosclerosis are characterized by retention of OCN (+) EPC within the coronary circulation, potentially leading to progressive coronary calcification rather than normal repair.

Topics: Adult; Blood Flow Velocity; Calcinosis; Cardiac Catheterization; Chemokine CXCL12; Coronary Artery Disease; Coronary Circulation; Endothelial Cells; Endothelium, Vascular; Female; Flow Cytometry; Humans; Interleukin-8; Male; Middle Aged; Osteocalcin; Stem Cells

Atherothrombotic disease in the coronary arteries leads to myocardial infarction (MI) through plaque rupture or erosion of the endothelium, the former mechanism predominating in men and the latter in women. Inflammation is a key feature of these processes, and the interplay between inflammation and matrix metalloproteinases (MMPs) in this context is not fully understood. In this study, we investigated the association between inflammatory markers and MMPs in men and women.. Blood samples were drawn 3 months after a first MI in 387 patients and 387 sex- and age-matched controls (82% men). C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, -18, tumour necrosis factor-alpha (TNF-alpha), macrophage chemoattractant protein-1 (MCP-1), MMP-1, -3 and -9 were measured. Coronary angiography was performed in 243 of the patients, and they were classified into 0-, 1-, 2- or 3-vessel disease groups.. CRP, IL-6, -8, -18 and TNF-alpha were higher, and MMP-3 and -9 were lower, in patients than in controls. A greater proportion of women (49%) had 0-vessel disease than men (16%, p<0.0001). A gender specific pattern of associations between inflammatory markers and MMPs was found as IL-6 (r(S)=0.29, p<0.05), IL-18 (r(S)=0.34, p<0.01) and MCP-1 (r(S)=0.35, p<0.01) correlated with MMP-3 in female patients, whereas CRP (r(S)=0.23, p<0.0001), IL-6 (r(S)=0.13, p<0.05) and IL-8 (r(S)=-0.21, p<0.01) correlated with MMP-9 in male patients.. The present study demonstrates different patterns of association between inflammatory markers and MMPs in men and women, strengthening the hypothesis of gender specific differences in pathophysiological mechanisms of MI.

Topics: Biomarkers; C-Reactive Protein; Chemokine CCL2; Coronary Artery Disease; Female; Humans; Interleukin-18; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Myocardial Infarction; Sex Characteristics; Tumor Necrosis Factor-alpha

Recently, there has been an increasing in the impact of oral health on atherosclerosis and subsequent cardiovascular disease. The aim of this study is to investigate the association between chronic periodontitis and cardiovascular risk markers.. Forty patients with periodontitis and 40 healthy gender-, body mass index-, and age-matched individuals were compared by measuring total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, levels of cytokines, antibodies against oxidized low-density lipoprotein, thiobarbituric acid reactive substances, total and differential white blood cell counts, and the non-linear index of refraction.. The levels of triglycerides and high-density lipoprotein in periodontitis patients were significantly higher and lower, respectively (P = 0.002 and P = 0.0126), compared to controls. Total cholesterol, low-density lipoprotein, and lipid peroxide levels were the same in both groups (P = 0.2943, P = 0.1284, and P = 0.067, respectively). Interleukin (IL)-6 and -8, antibodies against oxidized low-density lipoprotein, and leukocyte and neutrophil counts were significantly higher in periodontitis patients (P <0.05). The value of the non-linear index of refraction of low-density lipoprotein solutions was higher in the controls (P = 0.015) compared to individuals with periodontitis.. Our results confirmed and further strengthened the suggested association between coronary artery disease and periodontitis.

Topics: Adult; Age Factors; Antibodies; Body Mass Index; Case-Control Studies; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Chronic Periodontitis; Coronary Artery Disease; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Interleukin-6; Interleukin-8; Leukocyte Count; Lipid Peroxides; Lipoproteins, LDL; Male; Middle Aged; Neutrophils; Oxidation-Reduction; Refractometry; Risk Factors; Sex Factors; Thiobarbituric Acid Reactive Substances

Atherosclerosis is an inflammatory disease in which interferon (IFN)-gamma, the signature cytokine of Th1 cells, plays a central role. We investigated whether interleukin (IL)-17, the signature cytokine of Th17 cells, is also associated with human coronary atherosclerosis.. Circulating IL-17 and IFN-gamma were detected in a subset of patients with coronary atherosclerosis and in referent outpatients of similar age without cardiac disease but not in young healthy individuals. IL-17 plasma levels correlated closely with those of the IL-12/IFN-gamma/CXCL10 cytokine axis but not with known Th17 inducers such as IL-1beta, IL-6, and IL-23. Both IL-17 and IFN-gamma were produced at higher levels by T cells within cultured atherosclerotic coronary arteries after polyclonal activation than within nondiseased vessels. Combinations of proinflammatory cytokines induced IFN-gamma but not IL-17 secretion. Blockade of IFN-gamma signaling increased IL-17 synthesis, whereas neutralization of IL-17 responses decreased IFN-gamma synthesis; production of both cytokines was inhibited by transforming growth factor-beta1. Approximately 10-fold fewer coronary artery-infiltrating T helper cells were IL-17 producers than IFN-gamma producers, and unexpectedly, IL-17/IFN-gamma double producers were readily detectable within the artery wall. Although IL-17 did not modulate the growth or survival of cultured vascular smooth muscle cells, IL-17 interacted cooperatively with IFN-gamma to enhance IL-6, CXCL8, and CXCL10 secretion.. Our findings demonstrate that IL-17 is produced concomitantly with IFN-gamma by coronary artery-infiltrating T cells and that these cytokines act synergistically to induce proinflammatory responses in vascular smooth muscle cells.

Topics: Adult; Aged; CD4-Positive T-Lymphocytes; Cells, Cultured; Chemokine CXCL10; Coronary Artery Disease; Coronary Vessels; Female; Gene Expression Regulation; Humans; Inflammation Mediators; Interferon gamma Receptor; Interferon-gamma; Interleukin-17; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Receptors, Interferon; Receptors, Interleukin-17; Signal Transduction; T-Lymphocyte Subsets; Transforming Growth Factor beta1; Vasculitis

Plasma inflammatory markers have been shown to be predictors for cardiovascular risk, however, there is no study where the levels of plasma circulatory markers have been evaluated in coronary artery disease patients (CAD pts) positive for C. pneumoniae IgA and high sensitive C-reactive protein (hsCRP) which may help in better understanding of disease pathogenesis. A total of 192 patients and 192 controls attending the Cardiology Outpatient Department of Safdarjung Hospital were enrolled. The levels of plasma circulatory inflammatory markers were evaluated by ELISA. The levels of circulatory plasma markers (IL-4, IL-8, IL-13, ICAM-1, and VCAM-1) were significantly higher, whereas, levels of IL-10 and IFN-gamma were significantly lower in CAD pts compared to healthy controls. The levels of IL-4, IL-8, and ICAM-1 (P = .007, .015, and .048) were significantly higher, however, IL-10 and IFN-gamma were significantly lower (P < .001, < .001) in C. pneumoniae IgA positive CAD pts. The levels of IL-4, IL-8, IL-13, ICAM-1, and VCAM-1 were higher but not significant and levels of IL-10 and IFN-gamma were significantly (P < .001, < .001) lower in hsCRP positive CAD pts. Our study suggested that circulatory cytokines, namely, IL-4, IL-8, and adhesive molecules like ICAM-1 were enhanced after infection with C. pneumoniae whereas in contrast to this IL-10 and IFN-lambda were lowered. Suggesting the important role of these cytokines in progression of CAD.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Cell Adhesion Molecules; Chlamydophila Infections; Coronary Artery Disease; Cytokines; Female; Humans; India; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-4; Interleukin-8; Male; Middle Aged; Vascular Cell Adhesion Molecule-1

Although many studies have shown that the metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) both are associated with chronic inflammatory state and are risk factors for coronary artery disease (CAD), it is still unclear which condition is a more important contributor to the increased production of inflammatory chemokines. The purpose of this study was to assess monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) levels and their association with insulin resistance and adiponectin concentrations in CAD patients, who were categorized as having T2DM, MS, or neither.. CAD male patients were categorized into three groups: 24 non-obese patients with T2DM (D), 24 obese patients with MS (M) and 24 patients without T2DM or MS (W). 20 healthy subjects were selected as controls (C). Insulin resistance was assessed by the HOMA-IR method, but serum MCP-1, IL-8, and adiponectin levels were measured by xMAP technology.. Serum levels of MCP-1 and IL-8 in D and M groups were increased in comparison with W and C groups (p<0.001, p<0.01), but the increase in the M group was significantly higher than that in the D group (p<0.05, p<0,001), besides MCP-1 and IL-8 concentrations were correlated with HOMA-IR indexes (r=0.52; r=0.49, p<0.0001) and adiponectin levels (r=-0.59, p<0.0001). The M group demonstrated a diminution in the adiponectin level (p<0.01) and pronounced increase of HOMA-IR in comparison with the other three groups (p<0.01).. Obese CAD patients with MS have a more pronounced increase of MCP-1, IL-8 and HOMA-IR and more decreased adiponectin levels than non-obese CAD patients without MS.

Topics: Adiponectin; Adult; Aged; Biomarkers; Chemokine CCL2; Coronary Artery Disease; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Interleukin-8; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Factors

Atrial fibrillation (AF) is the most frequently encountered postoperative arrhythmic complication after coronary artery bypass graft (CABG). There is increasing evidence to support the influence of inflammation in the pathogenesis of AF. The aim of the present study was to investigate the relation of postoperative new AF and systemic inflammatory changes after CABG.. A total of 113 CABG patients were recruited in the present study. Holter data from 24-hour electrocardiography were collected from 1 day before the operation to postoperative day 2 (POD2). AF was registered as positive if any AF event occurred. Serum cytokine, including interleukin (IL)-6, IL-8, and IL-10 were analyzed before and after surgery.. The overall incidences of postoperative AF and sustained AF were 36.3% and 31.9%, respectively. Patients with postoperative AF had longer respiratory treatment, intensive care unit treatment, and inotropic medication periods. Similar concentrations of serum IL-6 were found after surgery in patients with and without AF. The concentrations of serum IL-8 was significantly higher at 2 hours and on POD1 and POD2 in patients with postoperative AF. The concentration of serum IL-10 was significantly higher on POD1 in patients with postoperative AF.. Postoperative AF in CABG patients is associated with a more complicated postoperative outcome. Higher concentrations of serum IL-8 in CABG patients with postoperative AF suggested that an influence of inflammation in the pathogenesis postoperative AF after open heart surgery.

Topics: Aged; Atrial Fibrillation; Cardiopulmonary Bypass; Cohort Studies; Coronary Artery Bypass; Coronary Artery Disease; Female; Humans; Inflammation; Interleukin-10; Interleukin-8; Male; Middle Aged; Risk Factors

Patients with advanced coronary artery disease (CAD) have an unfovourable prognosis. Therefore, early identification of this high-risk group is important.. To asses the utility of clinical, electrographic and echocardiographic parameters, supported by novel atherogenesis markers, to identify patients with triple vessel coronary artery disease (CAD).. The study group comprised 37 patients (29 males, mean age 64+/-8 years) suffering from multivessel CAD and a control group of 16 patients (8 males, mean age 60+/-10 years), in whom - despite typical stenocardial symptoms, positive exercise stress test and segmental contractility disturbances - coronary angiography did not reveal any haemodynamically significant CAD. Apart from coronary angiography, each patient had additionally an entire test panel performed assessing both the disease severity and the presence of other systemic dysfunction. Mean Gensini score in the study group was 91.9+/-43.8, including proximal Gensini score 52.6+/-45.6 and distal one 39.4+/-29.7.. Patients with triple vessel disease had a long history of angina (mean 84 months), of whom 30 (81%) experienced at least Q-wave myocardial infarction (MI). ECG changes typical for ischaemia were observed more often than in the control group. Also in patients with triple vessel disease echocardiography showed more escalated segmental contractility disorders, and left ventricular ejection fraction in this group was significantly lower than in the control group (44 vs. 55%, p <0.001). There were significant differences between CAD patients and control groups with respect to serum levels of: adiponectin (10.5+/-4.2 vs. 17.6+/-3 microg/ml, p=0.001), resistin (13.7+/-6.1 vs. 7.2+/-2.4 ng/ml, p=0.007), TNF-alpha (4.2+/-2.9 vs. 2.1+/-1.1 pg/ml, p=0.02) and IL-8 (18.4+/-4.1 vs. 12.2+/-4.1 pg/ml, p=0.008). Significant differences were also noted in lipid profile (total cholesterol: 201+/-47.1 vs. 183+/-18 mg/dl, NS; HDL cholesterol: 45+/-8.5 vs. 54+/-11 mg/dl, p=0.005; LDL cholesterol: 126.1+/-46.9 vs. 102+/-29 mg/dl, p=0.004), NT-proBNP [516 (174-1426) vs. 187 (39-573) pg/ml, p=0.02] and fasting blood glucose levels (97+/-14 vs. 94+/-11 mg/dl, p=0.03). Significantly lower serum adiponectin levels were observed in men and tobacco smokers.. Medical history, supported by interpretation of selected, routine imaging studies and novel biochemical markers, such as adiponectin, resistin, TNF-alpha, IL-8 or NT-proBNP, seem to be the key factors when assessing the risk of presence of advanced coronary artery atherosclerosis.

Topics: Adiponectin; Biomarkers; Cholesterol, HDL; Cholesterol, LDL; Comorbidity; Coronary Angiography; Coronary Artery Disease; Echocardiography; Electrocardiography; Female; Humans; Interleukin-8; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Resistin; Smoking; Tumor Necrosis Factor-alpha

Angioplasty with stent placement is commonly used to treat coronary atherosclerosis. However, 20-40% of stainless steel stents restenose within 6 months via a prolonged inflammatory response mediated by monocytic infiltration and cytokine secretion. In the current study, we tested a hypothesis that blood flow and monocytes interact to alter stent corrosion. We assessed the effects of THP1 monocytes on the corrosion rate of 316L stainless steel (316LSS) under shear stress (0.5-50 dyn/cm(2)). In addition, THP1 cytokine secretion was determined using cytokine arrays and ELISA analyses. Data were compared using ANOVA and Tukey post hoc analysis (alpha = 0.05). Monocytes significantly lowered 316LSS corrosion rates without limiting current density. However, shear stress alone did not alter the corrosion rate of 316LSS. THP1 cells adhered to the 316LSS surface at all flow rates. Exposure to the 316LSS/corrosion test under high fluid flow rates increased (>twofold) the secretion of 7 of the 42 cytokines tested (angeogenin, GRO, I309, interleukin 8, interleukin 6, interleukin 1beta, and macrophage chemoattractant protein-1). Each of these cytokines play a role in wound healing, macrophage differentiation, and cell proliferation, all hallmarks of in-stent restenosis. Furthermore, only IL8 levels were significantly higher than any of the system controls during the 316LSS/corrosion test conditions. The IL8 levels from the 316LSS/corrosion tests were not significantly different from the +LPS control. Together, these data suggest that monocytic cells maybe activated by exposure to 316LSS stents and could contribute to in-stent restenosis and altered corrosion of the stent.

Topics: Analysis of Variance; Angioplasty, Balloon, Coronary; Biocompatible Materials; Blood Flow Velocity; Cell Line; Coronary Artery Disease; Coronary Restenosis; Corrosion; Cytokines; Electrochemistry; Humans; Interleukin-8; Lipopolysaccharides; Materials Testing; Monocytes; Shear Strength; Stainless Steel; Stents; Stress, Mechanical

Of late, inflammatory reactions have been considered to play an important part in the development of atherosclerosis. Acute-phase inflammatory reaction, being initially a protective response directed within the homeostasis system towards lesion repair, may by itself due to various factors favor the development of pathological processes. Considering the role played by inflammation in the development of atherosclerosis, and inflammatory activity in obesity and diabetes mellitus (DM), a range of common and interrelated elements of these processes may be marked out. These are acute phase proteins and cytokines. Insulinoresistance, being the common precursor of obesity and DM, plays the key role in vascular lesion. The use of cytokine activity index seems to be a promising method of revealing patients with high risk of atherosclerosis.

Topics: Aged; Coronary Artery Disease; Cytokines; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Interferon-gamma; Interleukin-6; Interleukin-8; Middle Aged; Obesity; Tumor Necrosis Factor-alpha

CXC ligand 16 (CXCL16) may be involved in inflammation and lipid metabolism, and we hypothesized a role for this chemokine in coronary artery disease (CAD).. We performed clinical studies in CAD patients as well as experimental studies in cells with relevance to atherogenesis [i.e. endothelial cells, vascular smooth muscle cells (SMC), and peripheral blood mononuclear cells (PBMC)]. We also examined the ability of HMG-CoA reductase inhibitors (statins) to modulate CXCL16 levels both in vivo and in vitro. Our main findings were: (i) patients with stable (n = 40) and unstable (n = 40) angina had elevated plasma levels of CXCL16 compared with controls (n = 20); (ii) low-dose simvastatin (20 mg qd, n = 15) and high-dose atorvastatin (80 mg qd, n = 9) down-regulated plasma levels of CXCL16 during 6 months of therapy; (iii) in vitro, atorvastatin significantly decreased the interleukin (IL)-1beta-mediated release of CXCL16 from PBMC and endothelial cells; (iv) attenuating effect of atorvastatin on the IL-1beta-mediated release of CXCL16 in PBMC seems to involve post-transcriptional modulation as well as down-regulation of CXCL16 release through inhibition of the protease a disintegrin and metalloproteinase 10 (ADAM10); (v) soluble CXCL16 increased the release of IL-8, monocyte chemoattractant peptide 1, and matrix metalloproteinases in vascular SMC and increased the release of IL-8 and monocyte chemoattractant peptide 1 in PBMC, with particularly enhancing effects in cells from CAD patients.. Our findings suggest that soluble CXCL16 could be linked to atherogenesis not only as a marker of inflammation, but also as a potential inflammatory mediator.

Topics: Aged; Atorvastatin; Case-Control Studies; Cells, Cultured; Chemokine CCL2; Chemokine CXCL16; Chemokines, CXC; Coronary Artery Disease; Down-Regulation; Endothelium, Vascular; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Muscle, Smooth, Vascular; Pyrroles; Receptors, Scavenger; Simvastatin

Interleukin 8 is a strong chemoattractant factor for neutrophils and T lymphocytes. We investigated the potential influence of two common polymorphisms of the interleukin-8 gene, -251A/T, and 781C/T on susceptibility to coronary artery disease.. The hypothesis was tested by screening for the prevalence of the above polymorphisms in 241 angiographically diagnosed coronary artery disease patients compared to 157 selected controls with negative coronary angiography.. We found no significant differences between cases and controls concerning the allelic and genotypic frequencies of both the studied polymorphisms. Nevertheless, a statistically significant lower frequency of the AA containing genotypes was observed in cases presenting with acute coronary syndromes compared to asymptomatic subjects or patients with stable coronary artery disease (OR = 0.44, 95%CI: 0.2-0.98, p = 0.04). The strongest statistical significance was observed in the AA(251)TT(781) combined genotype (OR = 0.34, 95%CI: 0.14-0.85, p = 0.02).. Our results suggest that the genetic diversity of the interleukin-8 gene influences the clinical manifestation of CAD.

Topics: Aged; Base Sequence; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Female; Genetic Predisposition to Disease; Genetics, Population; Genotype; Humans; Interleukin-8; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic

Accumulating evidence support a role of neutrophils in coronary artery disease (CAD). However little is known about the action of neutrophils at a local inflammatory site represented by an atherosclerotic plaque. To gain insight into these issues, we applied a skin blister model that permits analyses of in vivo transmigrated neutrophils. We hypothesised that the chronic inflammation in stable CAD mediates priming of neutrophils that impacts the out-come of neutrophil action at an inflammatory site. Thirteen patients with angiographically verified CAD were eligible for study entry together with 13 age and sex matched controls. Markers of inflammation (IL-6 and CRP), neutrophil activation (IL-8 and MMP-9/NGAL), and functional aspects (CD11b up-regulation and intracellular H(2)O(2) production) of peripheral and in vivo transmigrated neutrophils were studied. Systemic IL-8 and MMP-9/NGAL concentrations were significantly increased in patients indicating a primed state in circulating neutrophils. In vivo transmigrated neutrophils in stable CAD patients had an increased propensity to release MMP-9/NGAL and a reduced capacity to up-regulate CD11b and to produce hydrogen peroxide. These aberrations at the inflammatory site may be a consequence of a primed state of circulating neutrophils and point towards potential mechanisms whereby neutrophils at a local inflammatory site may contribute to the pathogenesis of CAD.

Topics: Acute-Phase Proteins; Adult; Aged; Blister; C-Reactive Protein; CD11b Antigen; Cell Movement; Coronary Artery Disease; Female; Humans; Interleukin-6; Interleukin-8; Leukocyte Count; Lipocalin-2; Lipocalins; Male; Matrix Metalloproteinase 9; Middle Aged; Neutrophil Activation; Proto-Oncogene Proteins; Respiratory Burst; Skin; Up-Regulation

Although the participation of inflammation in atherogenesis is widely recognized, the identification of the different components has not been clarified. In particular, the role of inflammation in plaque destabilization is not fully understood.. Our main findings were as follows: (1) In a microarray experiment, we identified visfatin, one of the most recently identified adipokines, as a gene that was markedly enhanced in carotid plaques from symptomatic compared with plaques from asymptomatic individuals. This finding was confirmed when carotid plaques from 7 patients with asymptomatic and 14 patients with symptomatic lesions were examined with real-time reverse transcription polymerase chain reaction. (2) Immunohistochemistry showed that visfatin was localized in areas that were rich in lipid-loaded macrophages. (3) The relationship between visfatin and unstable lesions was also found in patients with coronary artery disease, demonstrating a strong visfatin immunostaining in lipid-rich regions within the material obtained at the site of plaque rupture in patients with acute myocardial infarction. (4) Both oxidized low-density lipoprotein and tumor necrosis factor-alpha increased visfatin expression in THP-1 monocytes, with a particularly enhancing effect when these stimuli were combined. (5) Visfatin increased matrix metalloproteinase-9 activity in THP-1 monocytes and tumor necrosis factor-alpha and interleukin-8 levels in peripheral blood mononuclear cells. Both of these effects were abolished when insulin receptor signaling was blocked.. Our findings suggest that visfatin should be regarded as an inflammatory mediator, localized to foam cell macrophages within unstable atherosclerotic lesions, that potentially plays a role in plaque destabilization.

Topics: Aged; Angina, Unstable; Atherosclerosis; Carotid Artery Diseases; Cell Line; Coronary Artery Disease; Cytokines; Female; Gene Expression Regulation; Humans; Immunohistochemistry; Inflammation; Interleukin-8; Macrophages; Male; Matrix Metalloproteinase 9; Middle Aged; Monocytes; Nicotinamide Phosphoribosyltransferase; Tumor Necrosis Factor-alpha

We investigated the association of several chemokines with the risk of stable coronary heart disease (CHD) in a large case-control study after adjustment for other established risk factors. Furthermore, we analyzed their correlation with various acute-phase proteins, inflammation-associated cytokines, and an adhesion molecule.. We included 312 patients aged 40 to 68 years with angiographically confirmed and stable CHD and 472 age- and gender-matched controls in this study. The main outcome measure was the odds ratio (OR) for CHD associated with increased levels of interferon (INF)-inducible protein of 10 kd (IP-10), interleukin (IL)-8, regulated on activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammation protein 1alpha (MIP-1alpha), or eotaxin determined by rigidly evaluated sandwich ELISAs. Serum levels of IP-10 and IL-8 were higher, and serum levels of RANTES were lower in CHD patients when compared with age- and gender-matched controls. In addition, values in the second and top tertile of IP-10 and IL-8 were associated with an increased OR for CHD when compared with values in the bottom tertile [OR for IP-10 (top tertile) was 2.62 (95% CI, 1.79 to 3.85) in the age- and gender-adjusted model and 1.93 (95% CI, 1.23 to 3.04) in the fully adjusted model, and for IL-8, the OR was 1.77 (95% CI, 1.20 to 2.59) and 1.53 (95% CI, 0.98 to 2.39), respectively]; increased RANTES values were associated with a lower OR for CHD [OR, 0.67 (95% CI, 0.47 to 0.96) and 0.61 (95% CI, 0.40 to 0.94)]. Furthermore, positive correlations of IP-10 and IL-8 with several acute-phase proteins or inflammation-associated cytokines were evident, and positive correlations for IP-10 plasma viscosity and intercellular adhesion molecule 1 were also present.. The current study suggests that there may be no universal upregulation of chemokines in CHD-associated inflammation but different upregulation of IP-10 and IL-8 versus downregulation of RANTES; there was no clear disease association for MCP-1, MIP-1alpha, or eotaxin.

Topics: Acute-Phase Proteins; Adult; Aged; Biomarkers; Case-Control Studies; Chemokine CCL11; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Chemokine CCL5; Chemokine CXCL10; Chemokines; Chemokines, CC; Chemokines, CXC; Coronary Artery Disease; Coronary Disease; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Macrophage Inflammatory Proteins; Male; Middle Aged; Risk Factors; Up-Regulation; Vasculitis

Toll like receptors (Tlr) are essential in activation of the innate immune system. We recently described that peptidoglycan, an exogenous Tlr2 specific ligand, is present in human atherosclerotic plaques and associated with histological markers for plaque vulnerability. Also, endogenous Tlr2 ligands can be expressed in atherosclerotic tissues. Here, we determined whether Tlr2 stimulation promotes pro-inflammatory cytokine/chemokine production in vitro and augments neointima formation and development of atherosclerotic plaques in vivo.. We detected Tlr2 using Western blot and RT-PCR in human coronary arteries and primary adventitial fibroblasts. RNAse protection assay demonstrated significant induction of IL-1, IL-6, IL-8 and MCP-1 mRNA after Tlr2 stimulation in human adventitial fibroblasts in vitro. ELISA demonstrated induction of IL-6, IL-8 and MCP-1. In vivo application of Pam(3)Cys-SK(4), a synthetic Tlr2 ligand, on femoral arteries of C57BL/6 wild type (WT) mice using a peri-adventitial cuff, significantly enhanced neointima formation compared to control arteries. This increased inflammatory response was not observed in Tlr2 knockout (Tlr2-/-) mice. In ApoE knockout mice (ApoE-/-), application of the same Tlr2 ligand led to a significant increase in atherosclerotic plaque development.. Local arterial Tlr2 stimulation induced neointima and atherosclerotic plaque formation in mouse femoral arteries. Tlr2 stimulation may be an important mediator in arterial occlusive disease.

Topics: Animals; Apolipoproteins E; Blotting, Western; Chemokine CCL2; Coronary Artery Disease; Fibroblasts; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Ligands; Lipoproteins; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Neovascularization, Pathologic; Receptors, Cell Surface; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Toll-Like Receptor 2; Toll-Like Receptors; Tunica Intima

Chronic inflammation is one of the main underlying mechanisms in the development of coronary artery disease (CAD). We investigated the prognostic value of inflammatory markers for cardiac events occurring more than 6 months after percutaneous coronary intervention (PCI), i.e. late cardiac events, furthermore we investigated the temporal stability of these markers. Exhausted patients (234) recently treated by successful PCI were studied. Serum samples collected about 6 weeks after PCI (baseline), 6 and 18 months after baseline were analyzed for CRP, IL-6, tumour necrosis factor (TNF-alpha), IL-10, IL-1ra, IL-8 and neopterin. In the mean cardiac follow-up of 24 months, 25 late cardiac events occurred. Cox proportional hazards analysis was used to determine the prognostic value. Elevated concentrations of IL-6 at baseline and 6 months later increased the risk of late cardiac events (RR 3.9, CI 1.7-9.0, p 0.00 and RR 3.6, CI 1.6-8.5, p 0.00). Elevated concentrations of CRP and IL-10 at baseline also increased the risk of late cardiac events (RR 2.5, CI 1.1-5.7, p 0.04 and RR 2.5, CI 1.1-5.6, p 0.03) as did IL-1 receptor antagonist at 6 months (RR 2.6, CI 1.1-6.1, p 0.04). Temporal stability was high for most markers, but highest for IL-6. These results support the assumption that chronic inflammation is a pathophysiological mechanism in the development of CAD.

Topics: Angioplasty, Balloon, Coronary; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Fatigue; Follow-Up Studies; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-6; Interleukin-8; Middle Aged; Neopterin; Postoperative Complications; Predictive Value of Tests; Sialoglycoproteins; Tumor Necrosis Factor-alpha

The pathologic modifications characterizing vein graft disease resemble those observed in native arteriosclerosis, but in accelerated form. Although both disorders are considered to be inflammatory diseases, it remains to be determined whether diseased vein grafts and atherosclerotic coronary arteries differentially express inflammatory mediators. Therefore, we examined whether differences in the expression of proinflammatory cytokines by these two distinct vascular pathologies favor the accelerated inflammation within diseased vein grafts.. The messengerRNA expression of various cytokines (interleukin-1 beta [IL-1 beta], IL-6, IL-8, tumor necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma]) was quantified using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in tissue samples of native saphenous veins (NSV, n = 5), diseased coronary arteries (CAD, n = 25), and diseased vein grafts (VG, n = 13).. Native saphenous veins did not contain any detectable transcripts except for IFN-gamma. As expected, CAD was characterized by the expression of IL-1 beta, IL-6, IL-8, IFN-gamma, and TNF-alpha mRNA. Interestingly VG also expressed these mediators, but at markedly higher levels. Quantification by RT-PCR revealed that, compared with specimens from the CAD group, VG specimens contained 5.8 +/- 1.2 times, 286 +/- 22 times, and 29 +/- 7.3 times as many transcripts for the cytokines IL-1 beta, IL-6 and TNF-alpha, respectively, as well as 25 +/- 8.3 times more transcripts for the chemokine IL-8. In contrast, the expression of IFN-gamma transcripts did not differ among the groups.. The elevated expression of proinflammatory cytokine transcripts supports the hypothesis that diseased vein grafts, compared with atherosclerotic coronary arteries, are characterized by enhanced inflammatory activity that might accelerate atherosclerotic modifications. This may implicate new therapeutic strategies for the prevention of vein graft disease.

Topics: Aged; C-Reactive Protein; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Cytokines; Female; Humans; Immunohistochemistry; Inflammation Mediators; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Reoperation; Reverse Transcriptase Polymerase Chain Reaction; Saphenous Vein; Tumor Necrosis Factor-alpha; Veins

Cardiopulmonary bypass induces a rise in cytokines released by activated monocytes. The apolipoprotein E and the tumor necrosis factor beta polymorphisms are risk factors for atherosclerosis. The aim of the study was to investigate whether the genetic variants of apolipoprotein E (APOE*E4) and tumor necrosis factor beta (TNFB*A329G) affect cytokine release after cardiopulmonary bypass.. Thirty-eight patients underwent standard coronary artery bypass grafting procedures. Genotyping for APOE*E4 and TNFB*A329G was performed. Concentrations of interleukin 8 and tumor necrosis factor alpha were measured for 48 hours after surgery. Clinical data were collected prospectively.. Fourteen patients (37%) carried the combination non-APOE*E4/wild-type TNFB*A329, 12 patients (32%) showed non-APOE*E4/TNFB*A329G, 9 patients (24%) had APOE*E4/TNFB*A329G, and 3 patients (7%) had APOE*E4/wild-type TNFB*A329. Total amount of tumor necrosis factor alpha was significantly higher in patients carrying the combination APOE*E4/TNFB*A329 than in those carrying non-APOE*E4/wild-type TNFB*A329 (P <.0001). Clinical data were similar except for intubation time and amount of transfusion, which were significantly increased in patients with genetic polymorphisms (P =.022, P =.033).. Presence of TNFB*A329G polymorphism in addition to APOE*E4 variant is associated with significantly higher releases of interleukin 8 and tumor necrosis factor alpha, prolonged intubation, and increased transfusion relative to patients without genetic variants. Preoperative determination of APOE/TNFB genotypes in patients undergoing coronary artery bypass grafting may lead to additional perioperative measures to ameliorate systemic inflammatory response.

Topics: Aged; Alleles; Apolipoprotein E4; Apolipoproteins E; Cardiopulmonary Bypass; Coronary Artery Disease; Coronary Circulation; Cytokines; Female; Genetic Markers; Genetic Predisposition to Disease; Genotype; Humans; Inflammation Mediators; Interleukin-8; Lymphotoxin-alpha; Male; Middle Aged; Polymorphism, Genetic; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

CXC-chemokines may be involved in atherogenesis. Herein we examined the possible role of CXC-chemokines in the inflammatory interactions between oxidized (ox-) low-density lipoprotein (LDL), platelets and peripheral blood mononuclear cells (PBMC) in 15 patients with coronary artery disease (CAD) without 'traditional' risk factors and 15 carefully matched controls. Our main findings were: (a) ox-LDL stimulated the release of the CXC-chemokines interleukin (IL)-8, ENA-78 and GRO-alpha from PBMC, particularly in CAD. (b) In platelets, ox-LDL induced release of ENA-78 and, when combined with SFLLRN, also of GRO-alpha, with significantly higher response in CAD. (c) Platelet-rich plasma, especially when costimulated with ox-LDL, enhanced the release of IL-8 from PBMC, particularly in CAD patients. (d) Freshly isolated PBMC showed markedly increased IL-8 mRNA expression in CAD patients. Our findings suggest enhanced inflammatory interactions between ox-LDL, platelets and PBMC in CAD patients involving CXC-chemokine related mechanisms, possible contributing to atherogenesis in these and other CAD patients.

Topics: Adult; Aged; Arteriosclerosis; Blood Platelets; Case-Control Studies; Chemokine CXCL1; Chemokine CXCL5; Chemokines; Chemokines, CXC; Chemotactic Factors; Coronary Artery Disease; Gene Expression; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Leukocytes, Mononuclear; Lipoproteins, LDL; Male; Middle Aged; Risk Factors; RNA, Messenger

According to increasing experimental and clinical evidence the inflammatory processes take important part in the development of atherosclerosis and its complications. The aim of the study was to evaluate the concentrations of selected inflammatory (IL-6, IL-8, MCP-1 and TNF-alpha) and antiinflammatory (IL-10) cytokines in children and adolescents with atherosclerosis risk factors: obesity, hypertension and diabetes. We studied 64 children and adolescents aged 14.88 +/- 2.4 years. Children were divided into: group with obesity (n = 11), group with obesity accompanying by hypertension (n = 14), children with hypertension (n = 11) and diabetic group (n = 28). Control group consisted of 15 healthy children aged 15.3 yrs. The evaluation of studied cytokines was performed with the use of immunoenzymatic ELISA kits (R&D Systems). IL-6 concentration in the whole group was 5.7 +/- 19 pg/mL and was significantly higher than in controls--2.3 +/- 2.3 pg/mL (p = 0.04). The highest IL-6 level was found in obesity group--11 +/- 30 pg/mL (p = 0.02). Significant difference was also found in the group with obesity and hypertension--8.3 +/- 15 pg/mL (p = 0.046) and in diabetic children--6.5 +/- 14 pg/ml (0.046). Interleukin 8 level in whole group was 486 +/- 839 pg/mL and was not different from the control group--236 +/- 197 pg/mL. IL-10 level in the study group was 4.9 +/- 3 pg/mL and did not differ from controls--4.5 +/- 1.2 pg/mL. TNF-alpha level was significantly higher in whole study group--8.9 +/- 2.4 pg/mL (p = 0.04) compared to controls--8.0 +/- 4.9 pg/mL, and in children with obesity--9.5 +/- 1.5 pg/mL (p = 0.034) as well as in children with obesity and hypertension--9.6 +/- 3.1 pg/mL (p = 0.042). MCP-1 level did not differ between the studied groups (228 +/- 124 pg/mL in whole study group) and controls--182 +/- 46 pg/mL. Correlation analysis by Spearman showed significantly correlation between IL-6 and body mass index in the whole study group. TNF-alpha also correlated with body mass index.. Children and adolescents with obesity, obesity accompanying by hypertension and diabetes have elevated levels of IL-6 and TNF-alpha. IL-6 and TNF-alpha correlates with body mass index not only in obese but also in hypertensive, slim children. The elevated levels of cytokines (IL-6, TNF-alpha) in children with atherosclerosis risk factors (particularly obesity) can confirm the presence of inflammatory process in early phases of atherosclerosis.

Topics: Adolescent; Body Mass Index; Case-Control Studies; Chemokine CCL2; Child; Coronary Artery Disease; Cytokines; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypertension; Interleukin-10; Interleukin-6; Interleukin-8; Male; Obesity; Risk Factors; Tumor Necrosis Factor-alpha

Endothelial cell dysfunction has been implicated in the inflammatory response to cardiopulmonary bypass, and the upregulation of endothelial cell expression of adhesion molecules might promote leukocyte extravasation in vivo. Soluble endothelial cell adhesion molecules are increased after bypass. The aim of this study was to investigate the relationship between endothelial cell-surface expression of adhesion molecules and their concentration in plasma after coronary artery bypass grafting.. Ten patients undergoing coronary artery bypass with cardiopulmonary bypass had 5 plasma samples taken at defined intervals before, during, and after cardiopulmonary bypass. Plasma was incubated with human umbilical vein endothelial cell monolayers, and expression of E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 on the surface of human umbilical vein endothelial cell monolayers was measured by means of enzyme-linked immunosorbent assay. Plasma soluble adhesion molecules, C-reactive protein, interleukin 8, interleukin 10, transforming growth factor beta1, and neutrophil counts were determined for each patient.. Markers typical of acute inflammation (ie, interleukin 8, neutrophils, and C-reactive protein) were all increased after bypass. Soluble plasma intercellular and vascular cell adhesion molecule 1 (but not E-selectin) were increased after bypass. However, endothelial cell expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 (but not E-selectin) were significantly decreased by exposure to postbypass plasma. Additionally, postbypass plasma inhibited interleukin 1beta-stimulated endothelial cell expression of vascular cell and intercellular adhesion molecule 1. Interleukin 10 and transforming growth factor beta1, both of which are known to inhibit endothelial cell adhesion molecule expression, were respectively increased 10-fold and 3-fold (P <.05) after bypass.. Despite containing increased soluble intercellular and vascular cell adhesion molecule 1, postbypass plasma inhibits endothelial cell expression of intercellular and vascular cell adhesion molecule 1. Upregulated vascular expression of adhesion molecules might not be essential for endothelial activation after bypass.

Topics: Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Artery Disease; E-Selectin; Endothelium, Vascular; Humans; Intercellular Adhesion Molecule-1; Interleukin-1; Interleukin-8; Up-Regulation; Vascular Cell Adhesion Molecule-1

Monocytes play a prominent role in inflammation, coagulation and atherosclerosis by their ability to produce tissue factor (TF) and cytokines. The aim of the present study was to establish whether virus-infected monocytes initiate coagulation. In addition, the production of cytokines by monocytes may accelerate the chronic process of atherosclerosis and may contribute to coronary syndromes by eliciting plaque instability.. Monocytes were isolated by Vacutainer(R), BD Biosciences, Alphen aan den Rijn, Netherlands and subsequent magnetic cell sorting (MACS(R), Milteny Biotec, Bergish Gladbach, Germany). Coagulation times in normal pooled plasma and Factor VII-deficient plasma were measured after infection with cytomegalovirus (CMV), Chlamydia pneumoniae (Cp) and influenza A\\H1N1. Anti-TF antibodies were added to neutralize TF expressed on monocytes. Interleukins (IL) 6, 8 and 10 were measured in the supernatants.. Chlamydia pneumoniae- and CMV-infected monocytes decreased the clotting time by 60%, and influenza-infected monocytes by 19%, as compared to uninfected monocytes. Procoagulant activity was absent when Factor VII-deficient plasma or anti-TF antibodies were used. Monocytes produced both IL-6 and IL-8 after infection with CMV (317 pg mL-1 and 250 pg mL-1) or Cp (733 pg mL-1 and 268 pg mL-1). Similar results were obtained for influenza virus-infected monocytes, but the levels of both cytokines were 3-5-fold higher (1797 pg mL-1 and 725 pg mL-1). Interleukin-10 was not produced by infected monocytes.. The procoagulant activity of virus-infected monocytes is TF-dependent. Although influenza infection did not generate a significant reduction in clotting time, the pronounced expression of IL-6 and IL-8 may induce local and/or systemic inflammatory reactions, which may be associated with plaque rupture and atherosclerosis. The lack of production of the anti-inflammatory cytokine IL-10 may even accelerate these processes.

Topics: Antibodies; Chlamydophila Infections; Coronary Artery Disease; Cytomegalovirus Infections; Humans; Influenza A virus; Influenza, Human; Interleukin-10; Interleukin-6; Interleukin-8; Monocytes; Thromboplastin; Virus Diseases; Whole Blood Coagulation Time

Interleukin-8 (IL-8), a CXC chemokine that induces the migration and proliferation of endothelial cells and smooth muscle cells, is a potent angiogenic factor that may play a role in atherosclerosis. Previously, IL-8 has been reported in atherosclerotic lesions and circulating macrophages from patients with atherosclerosis. Therefore, we sought to determine whether IL-8 plays a role in mediating angiogenic activity in atherosclerosis.. Homogenates from 16 patients undergoing directional coronary atherectomy (DCA) and control samples from the internal mammary artery (IMA) of 7 patients undergoing bypass graft surgery were assessed for IL-8 content by specific ELISA, immunohistochemistry, and in situ hybridization for IL-8 mRNA. The contribution of IL-8 to net angiogenic activity was assessed using the rat cornea micropocket assay and cultured cells. IL-8 expression was significantly elevated in DCA samples compared with IMA samples (1.71+/-0.6 versus 0.05+/-0.03 ng/mg of total protein; P<0.01). Positive immunolocalization of IL-8 was found exclusively in DCA tissue sections, and it correlated with the presence of factor VIII-related antigen. In situ reverse transcriptase polymerase chain reaction revealed the expression of IL-8 mRNA in DCA tissue. Corneal neovascular response, defined by ingrowth of capillary sprouts toward the implant, was markedly positive with DCA pellets, but no constitutive vessel ingrowth was seen with IMA specimens. Neutralizing IL-8 attenuated both the in vivo corneal neovascular response and the in vitro proliferation of cultured cells.. The results suggest that, in human coronary atherosclerosis, IL-8 is an important mediator of angiogenesis and may contribute to plaque formation via its angiogenic properties.

Topics: Angina Pectoris; Animals; Atherectomy, Coronary; Cells, Cultured; Cornea; Coronary Artery Bypass; Coronary Artery Disease; Coronary Vessels; DNA; Humans; Interleukin-8; Macrophages; Mammary Arteries; Neovascularization, Pathologic; Rats; Rats, Long-Evans; RNA, Messenger; Tissue Distribution; von Willebrand Factor

To validate the hypothesis that artery sites occluded with thrombi release pro-inflammatory cytokines, we measured concentrations of interleukin (IL)-6 and IL-8 in infarct-related coronary artery thrombi and atherosclerotic plaque specimens obtained with a transluminal extraction catheter (TEC) from cases of acute myocardial infarction (MI). Fifteen patients (group I) were enrolled in the study and four sets of samples were obtained (taken from the right atrium both before and after angioplasty, from infarct-related coronary artery thrombi and atherosclerotic plaque aspirated with a TEC and from the thoracic aorta aspirated with a TEC). Ten patients undergoing elective TEC served as controls (group II). IL-6 and IL-8 were measured in all patients by means of an enzyme-linked immunosorbent assay. Both IL-6 and IL-8 levels of infarct-related coronary artery samples in group I were significantly higher than in group II (mean +/- SEM, 15.3+/-4.5 vs. 3.8+/-1.2 pg/ml; P<0.01 and 44.0+/-2.4 vs. 15.6+/-0.6 pg/ml; P<0.01, respectively). The results suggest that pro-inflammatory cytokines originate from occluded coronary arteries in acute MI.

Topics: Angioplasty, Balloon, Coronary; Atherectomy, Coronary; Biomarkers; Cardiac Catheterization; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Suction

Chlamydia pneumoniae is a respiratory pathogen that has been associated with chronic inflammatory diseases such as asthma and atherosclerosis. Recent isolation of C. pneumoniae from human carotid and coronary atheromas provides additional support for a role of this organism in atherogenesis. We characterized the coronary strain C. pneumoniae A-03 by sequence analysis of the major outer membrane protein gene (omp1). In addition, the in vitro activities of A-03 and three respiratory strains of C. pneumoniae (BAL-16, TW-183, and T-2634) were examined in infected human umbilical vein endothelial cells (HUVEC) by analysis of the production of interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and soluble intercellular cell adhesion molecule 1 (sICAM-1). Sequence analysis of omp1 of C. pneumoniae A-03, compared to prototype strains TW-183 and AR-39, revealed five nucleotide changes resulting in nonsynonymous codons. Of interest was a nonconservative amino acid substitution (Ser to Pro) in position 61 of variable segment 1. In vitro, the extent of MCP-1, IL-8, and sICAM-1 production was dependent on the C. pneumoniae strain examined at low multiplicities of infection following 24 h of incubation. Strain A-03 displayed the lowest stimulatory activity in infected HUVEC, while T-2634 induced the highest levels of MCP-1, IL-8, and sICAM-1 among all strains examined. Heat-inactivated C. pneumoniae failed to stimulate production of these proteins by all strains tested. In contrast, only partial inhibition was observed by UV-inactivated organisms. Results from this study demonstrate that unlike prototype respiratory strains of C. pneumoniae, the coronary strain A-03 displays divergence in the omp1 gene. In addition, the stimulation of chemokines and adhesion molecules involved in the recruitment of leukocytes to sites of inflammation by C. pneumoniae may be important in the pathogenesis of diseases associated with this organism, including atherosclerosis.

Topics: Amino Acid Sequence; Bacterial Outer Membrane Proteins; Base Sequence; Cell Line; Chemokine CCL2; Chlamydophila pneumoniae; Coronary Artery Disease; Endothelium, Vascular; Genes, Bacterial; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Molecular Sequence Data