interleukin-8 and Angina--Unstable

The aim of this study was to assess the effects of glucose-insulin-potassium (GIK) solution on intraoperative cardiac cytokines and cardiac enzymes in coronary artery bypass surgery patients.. The study group consisted of 49 patients with unstable angina who required urgent CABG. Patients were randomized to a GIK (n = 25) or a non-GIK (n = 24) group. The GIK group received 500 ml of 30 % dextrose solution, containing 100 IU insulin and 80 mEq of potassium, at a rate of 1 ml x kg (-1) x h (-1). The control group received an equivalent rate of 5 % dextrose. Serum cytokine levels were measured in blood samples obtained from coronary sinus blood samples. Cardiac enzymes such as creatinin kinase (CK), myocardial band of creatinin kinase (CK-MB) and Troponin-T were measured immediately after operation and at 6, 24 and 48 hours after operation.. No patient in the two groups developed ECG or enzyme changes after surgery suggestive of acute myocardial infarction and myocyte damage. Interleukin-10 concentrations were greater in the GIK group (31.10 +/- 3.36) than in the non-GIK group (19.10 +/- 4.32) ( P < 0.05).. We conclude that a GIK solution increases the serum cardioprotective interleukin-10 concentrations in CABG patients with unstable angina pectoris. We found no significant difference in any of the other parameters respecting myocyte damage.

Topics: Angina, Unstable; Cardioplegic Solutions; Coronary Artery Bypass; Creatine Kinase, MB Form; Cytokines; Female; Glucose; Heart; Humans; Insulin; Interleukin-10; Interleukin-6; Interleukin-8; Intraoperative Period; Male; Middle Aged; Myocardium; Potassium

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

The aim of our study was to evaluate whether a single dose of cerivastatin at the time of admission of patients with unstable angina pectoris (UAP) or non-Q-wave myocardial infarction (NQMI) can influence the serum level of C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-8 (IL-8) 24 h later. Forty-four patients with rest chest pain and subendocardial ischemia on ECG were randomized to receive cerivastatin 0.3 mg at the time of admission (group C+) to standard therapy or to remain just on standard therapy (group C-). Blood samples for determination of troponin I (TI), CRP, IL-6 and IL-8 were collected at admission (entry level) and 24 h later (final level). Patients with non-physiological baseline levels of TI, as well as patients with progression to Q wave MI were excluded. All baseline, clinical and demographic data and final values of TI were comparable in the two groups. In patients treated with cerivastatin (group C+, n = 13) we observed decrease in the CRP level (-6.73 +/- 3.93 mg/L); on the other hand, in group C- (n = 17) the CRP level increased (+7.92 +/- 2.77 mg/L, p = 0.004). Similar differences were observed also in IL-6: in group C+ the level was significantly reduced as compared with the increase in group C- (-0.76 +/- 0.52 vs. 4.58 +/- 1.49 ng/L, p = 0.005). The level of IL-8 was not affected. Our results suggest that early treatment with cerivastatin can decrease the serum level of CRP and IL-6 in patients with UAP/NQMI; this might positively influence their prognosis. Nevertheless, further studies are needed to support this hypothesis.

Topics: Aged; Angina, Unstable; C-Reactive Protein; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Pyridines

Topics: Adult; Aged; Angina, Unstable; Biomarkers; Coronary Disease; Creatine Kinase; Female; Humans; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Myoglobin; Pilot Projects; Predictive Value of Tests

The role of endothelium in the progression of atheromasic disease has already been demonstrated. Endothelin-1 (ET-1) is released from endothelial cells during acute and chronic vascular damage and it appears to be the strongest vasoconstrictor agent known.The aim of this study is to investigate the amount of endothelial damage in patients with unstable angina (UA), as defined by serum levels of ET-1, to verify a possible correlation with increased ischaemic damage by evaluation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin 8 (IL-8) levels.Serum levels of ET-1, IL-8 and NT-proBNP obtained from 10 patients affected by low-risk UA were compared to those belonging to eight healthy subjects. In order to compare the laboratory data pertaining to the two populations, a Student's t-test and a Mann-Whitney U test were performed.Levels of ET-1, IL-8 and NT-proBNP in samples of peripheral blood of patients affected by UA were significantly elevated, compared with those of the control group. The linear correlation analysis demonstrated a positive and significant correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP in subjects affected by UA.Early elevated levels of ET-1, IL-8 and NT-proBNP in patients with UA show a coexistence between ischaemic insults and endothelial damages. A positive and significant linear correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP confirms that an increased ischaemic insult is correlated to inflammation signs and endothelium damage signs.In patients with UA, ischaemia is always associated with a systemic immuno-mediated activity induced by acute endothelial damage. We suggest early administration of ET-1-selective receptor blockers and anti-inflammatory drugs.

Topics: Acute Disease; Adult; Angina, Unstable; Endothelial Cells; Endothelin-1; Endothelium; Female; Humans; Immunologic Factors; Inflammation; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments

Inflammation is now believed to be responsible for coronary heart disease (CHD). This belief has stimulated the evaluation of various inflammatory markers for predicting CHD. This study was designed to investigate the association between four inflammatory cytokines (CD121a, interleukin [IL]-1β, IL-8, and IL-11) and CHD. Here, we evaluated 443 patients with CHD and 160 CHD-free controls who underwent coronary angiography. Cytokines were evaluated using flow cytometry, and statistical analyses were performed to investigate the association between cytokine levels and the risk of CHD. Patients with CHD had significantly higher levels of CD121a. The odds ratios for CHD according to increasing CD121a quartiles were 1.00, 1.47 [95% confidence interval (CI): 0.79-2.72], 2.67 (95% CI: 1.47-4.84), and 4.71 (95% CI: 2.65-8.37) in an age- and sex-adjusted model, compared to 1.00, 1.48 (95% CI: 0.70-3.14), 2.25 (95% CI: 1.10-4.62), and 4.39 (95% CI: 2.19-8.79) in a model that was adjusted for multiple covariates. A comparison of the stable angina, unstable angina, and acute myocardial infarction (AMI) subgroups revealed that patients with AMI had the highest CD121a levels, although IL-1β levels were similar across all groups. IL-8 levels were also increased in AMI patients, and IL-11 levels were higher in CHD patients than in non-CHD patients. Correlation analysis revealed a positive association between CD121a, IL-8, and the Gensini score. Together, the significant increase in CD121a levels among CHD patients suggests that it may be a novel inflammatory marker for predicting CHD.

Topics: Adult; Aged; Aged, 80 and over; Angina, Stable; Angina, Unstable; Biomarkers; Case-Control Studies; Coronary Disease; Female; Humans; Inflammation Mediators; Interleukin-11; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Receptors, Interleukin-1 Type I

Some inflammatory cytokines and parameters of low density lipoproteins (LDL) oxidative modification were studied in blood of 250 acute coronary syndrome (ACS) patients--Siberian inhabitants, men and women with myocardial infarction (MI) or unstable angina on first, tenth and thirtieth days of disease. The inflammatory biomarkers in men and women with MI are: increased concentrations of interleukin (IL)-6, IL-8 and C-reactive protein (CRP), especially on the first day of disease. The most significant inflammatory biomarker of ACS is increased CRP level, especially in women. Oxidative biomarkers in men with ACS are increased basal level of LDL lipid peroxidation (LPO) products and decreased LDL resistance to oxidation. Inflammatory-oxidative biomarkers IL-6, IL-8, CRP and basal level of LDL LPO products are correlated and independently associated with MI.

Topics: Aged; Angina, Unstable; Biomarkers; C-Reactive Protein; Female; Humans; Interleukin-6; Interleukin-8; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Myocardial Infarction; Risk Factors; Sex Factors; Siberia; Time Factors

The time course of inflammatory reaction markers in the blood of patients with unstable angina was studied during therapy including arixtra. Plasma concentration of monocytic chemotaxic protein-1 (MCP-1) decreased on days 2 and 3 in patients receiving arixtra and a trend to an increase in MCP-1 concentration was observed on day 7 after the drug was discontinued. After 1 month, MCP-1 level decreased in all patients. The concentration of highly sensitive C-reactive protein also decreased 1 month after the disease onset; no changes in the concentrations of IL-8 and IL-2 receptor α-subunit were detected during these periods. It seems that arixtra is characterized by an anti-inflammatory effect manifesting by reduction of plasma chemokine MCP-1 concentration.

Topics: Aged; Angina, Unstable; Biomarkers; C-Reactive Protein; Chemokine CCL2; Female; Fondaparinux; Humans; Inflammation; Interleukin-2 Receptor alpha Subunit; Interleukin-6; Interleukin-8; Male; Middle Aged; Polysaccharides

The interaction between inflammatory cytokines and endothelial cells is a critical step in atherogenesis leading to endothelial dysfunction and inflammation. We have previously reported that the tumor necrosis factor superfamily member LIGHT could be involved in atherogenesis through its ability to promote vascular inflammation. In the present study we identified proteinase-activated receptor (PAR)-2 as an inflammatory mediator that was markedly enhanced by LIGHT in endothelial cells. We also found that LIGHT acted synergistically with PAR-2 activation to promote enhanced release of the proatherogenic chemokines interleukin-8 and monocyte chemoattractant protein-1, underscoring that the interaction between LIGHT and PAR-2 is biologically active, promoting potent inflammatory effects. We showed that the LIGHT-mediated upregulation of PAR-2 in endothelial cells is mediated through the HVEM receptor, involving Jun N-terminal kinase signaling pathways. A LIGHT-mediated upregulation of PAR-2 mRNA levels was also found in human monocytes when these cells were preactivated by tumor necrosis factor alpha. We have previously demonstrated increased plasma levels of LIGHT in unstable angina patients, and here we show a similar pattern for PAR-2 expression in peripheral blood monocytes. We also found that LIGHT, LIGHT receptors, and PAR-2 showed enhanced expression, and, to some degree, colocalization in endothelial cells and macrophages, in the atherosclerotic plaques of ApoE(-/-) mice, suggesting that the inflammatory interaction between LIGHT and PAR-2 also may be operating in vivo within an atherosclerotic lesion. Our findings suggest that LIGHT/PAR-2-driven inflammation could be a pathogenic loop in atherogenesis potentially representing a target for therapy in this disorder.

Topics: Aged; Angina Pectoris; Angina, Unstable; Animals; Atherosclerosis; Cells, Cultured; Chemokine CCL2; Endothelial Cells; Endothelium, Vascular; Female; Gene Expression Regulation; Humans; Interleukin-8; JNK Mitogen-Activated Protein Kinases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Nitric Oxide Synthase Type III; Receptor, PAR-2; Receptors, Tumor Necrosis Factor, Member 14; Recombinant Fusion Proteins; Signal Transduction; Tumor Necrosis Factor Ligand Superfamily Member 14; Vasculitis

Topics: Angina, Unstable; C-Reactive Protein; Chemokines; Chemotaxis; Female; Humans; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-8; Male; NF-kappa B; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index

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

Atherosclerosis is a chronic inflammatory disease and interleukins are considered to play a key role in the chronic vascular inflammatory response that is typical of atherosclerosis. The serum levels of several of these cytokines have been found to positively correlate with coronary arterial disease and its sequelae.. The aim of our study was to evaluate the levels of a comparatively new cytokine IL-17, in patients with stable and unstable coronary artery disease in order to assess whether unstable coronary artery disease patients had higher IL-17 levels.. We analyzed the concentrations of IL-17, IL-6, IL-8 and IL-10 using enzyme-linked immunosorbent assay and heat-sensitive C-reactive protein using latex particle-enhanced immunoturbidimetry in 58 consecutive unselected patients divided into three groups: stable angina (n=14), unstable angina (n=24) and acute myocardial infarction (n=20). We further compared them with 20 healthy controls. These 58 patients were also angiographically studied and divided into two groups: simple lesion (n=22) and complex lesion (n=36), on the basis of the coronary plaque morphology.. Our results show increased concentrations of the proinflammatory cytokines IL-17, IL-6, IL-8 and heat-sensitive C-reactive protein, and decreased concentration of IL-10 in plasma of unstable angina and acute myocardial infarction patients. Plasma concentration of IL-17 was also positively correlated with plasma concentrations of IL-6 and heat-sensitive C-reactive protein. Our findings further showed that IL-17 values were higher in patients having angiographically visible complex types of lesions but no difference was observed between complex and simple lesion morphology patients.. In conclusion, these findings point towards a role of inflammation in the form of increased activity of IL-17, IL-6 and IL-8 in patients of unstable angina and acute myocardial infarction and thus suggest that IL-17-driven inflammation may play a role in the promotion of clinical instability in patients with coronary artery disease.

Topics: Angina, Unstable; Biomarkers; C-Reactive Protein; Coronary Angiography; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Interleukin-17; Interleukin-6; Interleukin-8; Male; Middle Aged; Prognosis; Severity of Illness Index

Inflammation is the most important mechanism of plaque disruption playing an essential role in acute coronary syndromes. It is controversial whether the inflammatory mediators are the cause or the result in the development of plaque rupture. Stimulation of interleukins increases adhesion molecules, fibrinogen and plasminogen activator inhibitors,which cause the activation of inflammation and thrombosis. However, the importance of interleukins in acute coronary syndromes has not been clearly defined. We did not find any article concerning relations between the levels of serum interleukin(IL)-1beta, IL-2, IL -8 and tumor necrosis factor (TNF)-alpha in patients with unstable angina pectoris (UAP). So the aim of this study was to determine the levels of serum I -1b, IL-2, IL-8 and TNF-alpha during the early stage of UAP.. Thirty-seven patients with UAP(12 females and 25 males; mean age, 57.5 +/- 9.7 years) within 6 h of admission and 20 healthy volunteers(eight females and 12 males; mean age, 51.3 +/- 6.3 years) were included in the study. IL-1beta, IL-2, IL-8 and TNF-alpha levels were measured using the enzyme-linked immunosorbent assay method. Patients with acute or chronic inflammation, renal failure or chronic heart failure were excluded from the study. The age, gender and risk factors of the study and control groups were similar. The levels of IL-1beta, IL-8 and TNF-alpha were significantly increased (p < /0.0001, p < /0.001 and p < /0.016, respectively) in patients with UAP. There was no difference of IL-2 levels between the UAP group and controls.. We detected high levels of IL-1beta, IL-8 and TNF-alpha in patients with UAP during early phase. We suggest that proinflammatory cytokines (e.g. IL-1beta,IL-8, TNF-alpha) may play an important role in the development of atherosclerosis and its complications.

Topics: Aged; Angina, Unstable; Case-Control Studies; Female; Humans; Interleukin-1; Interleukin-2; Interleukin-8; Male; Middle Aged; Reference Values; Tumor Necrosis Factor-alpha

Inflammation is an important phenomenon in atherosclerotic plaque growth and in plaque instability. Cytokines are nuclear mediators in the inflammatory response; some have proinflammatory and others anti-inflammatory roles. Proinflammatory cytokines have been associated with worse outcomes in unstable angina. The aims of this study were to determine the role of the anti-inflammatory cytokine interleukin (IL)-10 and the proinflammatory to anti-inflammatory ratios in the short-term prognosis of patients with unstable angina.. Serum levels of proinflammatory cytokines IL-1beta, IL-6, and IL-8, and of the anti-inflammatory cytokine IL-10 were determined on admission in 127 consecutive patients with severe unstable angina, and comparisons were made between patients who had cardiovascular events (death, nonfatal myocardial infarction, readmission for refractory angina) (n = 20) and patients without coronary events (n = 107) during a follow-up period of 3 months.. IL-10 levels were lower (0.67 +/- 1.13 vs 1.33 +/- 1.67 pg/mL, P =.04) and IL-8 levels were higher (3.6 +/- 2.41 vs 2.23 +/- 2.47 pg/mL, P =.029) in patients in whom cardiovascular events subsequently developed compared with those without events, with resulting higher proinflammatory to anti-inflammatory cytokine ratios in the former group, whereas no significant differences were seen in IL-1beta or IL-6 levels between the groups, except for the subgroup of patients with prolonged rest angina and persistent electrocardiographic changes. A greater ratio of IL-8 to IL-10 serum levels was observed in patients who had coronary events (28 +/- 25 vs 12 +/- 21, P =.007). The risk of subsequent coronary events increased in patients in the highest quartile of proinflammatory to anti-inflammatory cytokine ratio (IL-8/IL-10). Patients in the highest quartile had a relative risk 3.8 times higher than those in the lowest quartile (P =.01).. Lower levels of IL-10, with higher proinflammatory to anti-inflammatory cytokine ratios, were observed on admission in patients with unstable angina who subsequently had cardiovascular events. Higher levels of the anti-inflammatory cytokine IL-10 may be needed to provide protection in unstable angina.

Topics: Adult; Aged; Aged, 80 and over; Angina, Unstable; Biomarkers; Coronary Disease; Female; Follow-Up Studies; Humans; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Prognosis; Time Factors

The pathogenesis of atherosclerosis and acute coronary syndromes involves inflammation and immunological mechanisms. We hypothesized that patients with unstable angina may have an imbalance between inflammatory and anti-inflammatory cytokines.. Plasma levels of tumour necrosis factor (TNF)alpha and interleukin (IL)-10 were analyzed in 44 patients with stable angina, 29 patients with unstable angina and 20 controls. mRNA levels of these cytokines were analyzed in peripheral blood mononuclear cells (PBMC). We also studied the in vitro effects of IL-10 in PBMC from unstable angina patients.. Our main findings were: (1) the angina patients and particularly those with unstable disease had significantly raised TNFalpha in comparison with the controls, both at the protein and mRNA level; (2) in contrast, the levels of IL-10 were not different in the angina patients in comparison with the healthy controls, resulting in a markedly enhanced TNFalpha:IL-10 ratio, particularly in the unstable angina patients; (3) while exogenously added IL-10 markedly inhibited the release of TNFalpha, IL-8 and tissue factor as well as impairing the gelatinolytic activity and mRNA production of matrix metalloproteinase-9, it enhanced the tissue inhibitor of this metalloproteinase (i.e. TIMP-1) in PBMC from the unstable angina patients.. Patients with unstable angina appear to have an imbalance between TNFalpha and IL-10, possibly favouring inflammatory net effects. IL-10 may have beneficial effects on mechanisms that are important in plaque rupture and thrombus formation.

Topics: Adult; Aged; Angina Pectoris; Angina, Unstable; Case-Control Studies; Cells, Cultured; Female; Humans; Interleukin-10; Interleukin-8; Leukocytes, Mononuclear; Male; Matrix Metalloproteinase 9; Middle Aged; RNA, Messenger; Stimulation, Chemical; Thromboplastin; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha

Alterations of the immune system are now believed to play crucial role in the pathogenesis of atherosclerosis. The aim of this study was analysis of soluble forms of selectin-P and interleukin-8 levels in patients with different form of coronary heart disease.. In the study took part 18 patients with stable coronary heart disease, 20 patients with unstable coronary heart disease and 15 healthy persons from control group. Soluble selectin-P and interleukin-8 levels were measured in EDTA plasma with the use of enzyme immunoassay ELISA.. The level of soluble selectin-P was significantly higher in unstable coronary heart disease patients in comparison to the stable coronary heart disease patients (P < or = 0.01) and nonsignificantly higher in comparison to the control group. The level of interleukin-8 were significantly higher in unstable coronary heart disease patients in comparison to the stable coronary heart disease patients (P < or = 0.01) and in comparison to the control group (P < or = 0.02).. Our findings suggest that soluble form of selectin-P and interleukin-8 may be useful clinical predictors of unstable coronary heart disease. The assessment of the risk for the development of coronary heart disease requires further serial investigation.

Topics: Aged; Angina, Unstable; Biomarkers; Case-Control Studies; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-8; Male; Middle Aged; P-Selectin

The aim of the present study was to investigate inflammatory cytokine release and the interaction with platelets in patients with unstable angina (UA) after coronary angioplasty. In 50 patients with stable angina (SA) and 58 patients with UA, serial venous blood samples were obtained immediately before, and 30 minutes, 4, 12, 24, 48 and 72 hours, and 7 days after coronary angioplasty. Plasma concentrations of IL-8 and vWF were determined by immunoassay, while the expression of CD11 b/CD18 on monocytes and the expression of CD41 on platelets were assessed by flow cytometry. Differences in the baseline plasma concentrations of IL-8, vWF and CD11b/CD18, CD41 were found in the UA and SA groups before angioplasty (101.1 +/- 31.28 pg/mL to 55.8 +/- 17.24 pg/mL, 137.67 +/- 38.14% to 107.40 +/- 28.67% and 318.67 +/- 36.85 MFI to 240.72 +/- 28.43 MFI, 147.5 +/- 23.18 MFI to 104.43 +/- 26.68 MFI all p < 0.05). The peak plasma levels of IL-8 (172.24 +/- 37.82 pg/mL at 12 hours) and vWF (256 +/- 42.32% at 4 hours) significantly increased after coronary angioplasty (both p < 0.01), and were associated with significant time course increases in surface expression of CD11b/CD18 (p < 0.01) and CD41 (p < 0.01). The levels of plasma IL-8 and vWF were significantly higher pre- and post-procedure in UA patients with lesion type C compared to types A or B (p < 0.05), but there were no differences for pre-procedure in the SA group patients with different lesion types (p > 0.05). There were significant correlations between plasma IL-8 and monocyte CD11b/CD18, vWF and CD41 in the UA group (r = 0.5248, r = 0.6240 both p < 0.01, respectively). The findings demonstrate increases in plasma IL-8 and CD11b/CD18 as inflammatory mediators, vWF and CD41 as the abnormal coagulation activity may therefore yield a rationale for pharmacological anticytokines in patients with UA after coronary angioplasty.

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; CD18 Antigens; Cytokines; Female; Flow Cytometry; Humans; Interleukin-8; Macrophage-1 Antigen; Male; Middle Aged; Platelet Glycoprotein GPIIb-IIIa Complex; von Willebrand Factor

Chemokines play a pathogenic role in atherogenesis and plaque destabilization by activating and directing leukocytes into the atherosclerotic plaque. However, stromal cell-derived factor (SDF)-1 was recently found to have antiinflammatory effects, and we hypothesized that this chemokine could play a beneficial role in coronary artery disease.. Plasma levels of SDF-1alpha were significantly decreased in patients with stable (n=30) and unstable angina (n=30) compared with healthy control subjects (n=20), particularly in those with unstable disease. By flow cytometry and RNase protection assay, we found decreased surface expression but increased gene expression of the SDF-1alpha receptor CXCR-4 in peripheral blood mononuclear cells (PBMC) from patients with stable angina and patients with unstable angina. In vitro, SDF-1alpha (500 ng/mL) reduced both unstimulated and endotoxin/mitogen-stimulated mRNA and protein levels of monocyte chemoattractant protein-1, interleukin-8, matrix metalloproteinase-9, and tissue factor while increasing tissue inhibitor of metalloproteinases-1 in PBMC from patients with unstable angina. The SDF-1alpha-mediated suppression of monocyte chemoattractant protein-1 and interleukin-8 appears to involve cAMP/protein kinase A type I-dependent pathways. Finally, although SDF-1alpha suppressed the spontaneous release of these inflammatory mediators in unstable angina, enhancing effects were seen in unstimulated PBMC from healthy control subjects, possibly reflecting that PBMC in unstable angina are preactivated in vivo.. In contrast to several other chemokines, our findings suggest that SDF-1alpha, at least in high concentrations, may mediate antiinflammatory and matrix-stabilizing effects in unstable angina. These effects may promote plaque stabilization, and therapeutic intervention that enhances SDF-1alpha activity could potentially be beneficial in acute coronary syndromes.

Topics: Angina, Unstable; Anti-Inflammatory Agents; Cells, Cultured; Chemokine CCL2; Chemokine CXCL12; Chemokines, CXC; Cyclic AMP-Dependent Protein Kinases; Cytokines; Dose-Response Relationship, Drug; Extracellular Matrix; Female; Humans; Interleukin-8; Leukocytes, Mononuclear; Male; Matrix Metalloproteinase 9; Middle Aged; Receptors, CXCR4; RNA, Messenger; Thromboplastin; Tissue Inhibitor of Metalloproteinase-1

Both the hemostatic and inflammatory system are thought to play a role in the pathogenesis of acute coronary syndromes. However, their respective contribution and interrelationship remain unclear, therefore, we studied the relationship between activation of the coagulation system and proinflammatory activity in ischemic coronary syndromes.. Thrombin-antithrombin III (TAT), prothrombin fragments F1 + 2, fibrinopeptide A (FPA), interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured in 50 patients with unstable angina (UA), 60 patients with acute myocardial infarction (AMI) and in 50 patients with stable angina (SA).. FPA levels were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0015 and p < 0.0001), and were higher in patients with AMI than UA (p = 0.0013). Plasma IL-6 concentrations were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0020 and p < 0.001), and again were higher in AMI than UA (p = 0.001). Interestingly, FPA or IL-6 elevations on admission were found in different patients. In contrast, TAT, F1 + 2 and IL-8 levels were not different between the three groups.. IL-6 and FPA were shown to be independent predictive markers with equal discriminative power to distinguish stable (SA) from unstable (UA + AMI) patients. Moreover, hemostatic and inflammatory markers can be elevated independently in the acute phase of ischemic coronary syndromes.

Topics: Angina, Unstable; Antithrombin III; Biomarkers; Female; Fibrinopeptide A; Humans; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Prothrombin; Statistics, Nonparametric; Thrombin