interleukin-8 and Acute-Coronary-Syndrome

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

Myocardial infarction (MI) is the most common cause of cardiac injury in the Western world. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Inflammatory cytokines and vascular cell adhesion molecules (VCAM) promote adhesive interactions between leukocytes and endothelial cells, resulting in the transmigration of inflammatory cells into the site of injury. Low vitamin D levels are associated with higher prevalence of cardiovascular risk factors and a higher risk of MI. In this paper, we examine the effects of short-term vitamin D supplementation on inflammatory cytokine levels after an acute coronary syndrome. We recruited patients arriving to the hospital with an acute MI. All patients received optimal medical therapy and underwent a coronary catheterization. Half of the patients were randomly selected and treated with a daily supplement of vitamin D (4,000 IU) for 5 days. A short course of treatment with vitamin D effectively attenuated the increase in circulating levels of inflammatory cytokines after an acute coronary event. Control group patients had increased cytokine and cellular adhesion molecules serum concentrations after 5 days, while the vitamin D-treated group had an attenuated elevation or a reduction of these parameters. There were significant differences in VCAM-1 levels, C-reactive protein, and interleukin-6. There were trends toward significance in interleukin-8 levels. There were no significant differences in circulating levels of intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and tumor necrosis factor-α. These findings provide information on the anti-inflammatory effects of vitamin D on the vascular system and suggest mechanisms that mediate some of its cardioprotective properties. There is place for further studies involving prolonged vitamin D treatment in patients suffering from ischemic heart disease.

Topics: Acute Coronary Syndrome; Adult; Aged; C-Reactive Protein; Cardiac Catheterization; Coronary Vessels; Female; Finland; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Risk Factors; Vascular Cell Adhesion Molecule-1; Vitamin D; Vitamin D Deficiency

The study was designed to estimate activity of a series of anti-inflammatory markers (C-reactive protein (CRP), ceruloplasmin, haptoglobulin, interleukin (IL)-4, and IL-8) in the acute phase of acute coronary syndrome (ACS) and effect of beta-adrenoblocking therapy on their activity. The patients were divided into 2 groups: one was treated with beta-blocker metoprolol tartrate as a main component of ACS pharmacotherapy (n = 30), the other included the patients with absolute contraindications to bena-adrenoblockers (n = 15). Otherwise, patients of both groups received standard antianginal therapy including nitrates, anticoagulants, ACE inhibitors, and statins. The frequency of prescription of these drugs and coronary angioplasty was comparable in both groups. It was shown that patients with ACS have elevated levels of CRP, haptoglobulin and prooxidant marker ceruloplasmin.

Topics: Acute Coronary Syndrome; Adrenergic beta-1 Receptor Antagonists; Aged; Biomarkers; C-Reactive Protein; Ceruloplasmin; Female; Haptoglobins; Humans; Inflammation; Interleukin-4; Interleukin-8; Male; Metoprolol

The aim of this 12 months observational study was to investigate risk factors of major adverse coronary events, such as death or Q wave myocardial infarction due to stent thrombosis or in stent restenosis.. One hundred fifty four patients with ST segment elevation acute coronary syndrome were treated with percutaneous coronary intervention (PCI) and with implantation of metal stent. TIMI and CADILLAC scores were used for evaluation of initial risk. Blood levels of cytokines and sP selectin were measured on day 1 before PCI and on day 10 of hospitalization.. We proved that CADILLAC score was applicable for evaluation of prognosis in patients with acute coronary syndrome and ST segment elevation treated with coronary stenting. High levels of tumor necrosis factor during first 24 hours of acute coronary syndrome and interleikin 8 on day 10 after PCI were found to be risk factors of major adverse coronary events during subsequent 12 months. High sP selectin level on day 10 predicted stent thrombosis during long term follow up.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Biomarkers; Coronary Angiography; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Interleukin-8; Male; Middle Aged; P-Selectin; Platelet Aggregation Inhibitors; Predictive Value of Tests; Russia; Stents; Time Factors; Tumor Necrosis Factor-alpha

Acute coronary syndrome (ACS) is currently a leading cause of morbidity and mortality worldwide. This study aimed to screen critical genes and miRNAs involved in ACS.. Microarray data (access number GSE19339) was downloaded from Gene Expression Omnibus (GEO) database. After data preprocessing, we screened the differentially expressed genes (DEGs) using limma package and subsequently performed enrichment analysis using DAVID tool. The protein-protein interaction (PPI) network and transcription factor (TF)-miRNA-target gene regulatory network were visualized using Cytoscape software. Finally, the drug-gene interactions were predicted using DGIdb database.. A total of 425 DEGs were identified in ACS samples compared with healthy control samples. Functional enrichment analysis showed that DEGs were mainly involved in angiogenesis, inflammatory response and PI3K-Akt signaling pathway. IL6 and VEGFA were key nodes in PPI network. In addition, hsa-miR-29, hsa-miR-1, NFIC, NFKB1 and RELA were identified as key factors in TF-miRNA-target gene network. Finally, the prediction results revealed that VWF, CXCL8 and IL6 had higher degree than other genes.. IL6 and VEGFA might play major roles in ACS progression. Two miRNAs (hsa-miR-29 and hsa-miR-1) and three TFs (NFIC, NFKB1 and RELA) were critical genes involved in pathological process of ACS. VWF, CXCL8 and IL6 might be potential druggable genes for ACS therapy.

Topics: Acute Coronary Syndrome; Cluster Analysis; Databases, Genetic; Gene Regulatory Networks; Humans; Interleukin-6; Interleukin-8; MicroRNAs; Software; von Willebrand Factor

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

Coactivator-associated arginine methyltransferase 1 (CARM1) is essential for the activation of a subset of NF-кB-dependent genes, which code the chemokines triggering plaque vulnerability. Unstable atherosclerotic plaques lead to the onset of acute coronary syndrome (ACS). Therefore, we aimed to investigate whether CARM1 is involved in the pathogenesis of ACS and ascertain the regulatory mechanism of CARM1 expression at posttranscriptional level.. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood of 19 patients with ACS and 22 subjects with risk factors for coronary heart disease. Gene expression was determined by quantitative real-time PCR and Western blot. The effects of CARM1 and miR-15a on their target genes expression were assessed by gain-of-function and loss-of-function approaches.. PBMCs from patients with ACS showed higher levels of CARM1 mRNA and protein expression. The levels of CARM1 mRNA were positively correlated with three chemokines including interferon-inducible protein-10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), and interleukin-8 (IL-8) in PBMCs (CARM1 and IP-10: r=0.55, P=0.008; CARM1 and MCP-1: r=0.64, P=0.002; CARM1 and IL-8: r=0.55, P=0.008). Moreover, CARM1 regulated the transcription of these chemokines in human embryonic kidney 293T (HEK293T) cells. We also found that the levels of miR-15a were decreased by 37% in patients with ACS and miR-15a modulated CARM1 expression through targeted binding to CARM1 3'-UTR.. The present study demonstrated that CARM1 targeted by miR-15a played an important role in chemokine activation in the pathogenesis of ACS.

Topics: 3' Untranslated Regions; Acute Coronary Syndrome; Angina Pectoris; Blotting, Western; Case-Control Studies; Chemokine CCL2; Chemokine CXCL10; Gene Expression Regulation; HEK293 Cells; Humans; Inflammation; Interleukin-8; Leukocytes, Mononuclear; Male; MicroRNAs; NF-kappa B; Protein-Arginine N-Methyltransferases; Real-Time Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Transfection

Several lines of evidence indicate that increased inflammatory cytokine levels can be used for risk prediction in patients with acute coronary syndrome (ACS). This study therefore aimed to evaluate correlations between levels of soluble interleukin (IL)-2 receptor (sIL-2r), IL-6, and IL-8 and in-hospital incidence of acute heart failure (AHF) and left ventricular (LV) systolic dysfunction in the subacute phase of ACS. In 48 consecutive patients with ACS, circulating levels of sIL-2r, IL-6, and IL-8 were ascertained 72-96 h after onset of symptoms. Clinical data, LV function, and in-hospital incidence of AHF were also evaluated. IL-8 levels were significantly higher in patients with pulmonary edema (1,829 ± 2,496 vs 456 ± 624 pg/ml, p < 0.05); sIL-2r, IL-6, and IL-8 levels were increased proportionally to Killip class (r = 0.35, p < 0.05; r = 0.48, r = 0.47, p < 0.01) and in patients with LV ejection fraction (LVEF) < 30%. Levels of sIL-2r were inversely related to LVEF in subjects with acute myocardial infarction (r = -0.51, p < 0.05). Soluble IL-2r and IL-8 levels were related to mitral regurgitation severity (r = 0.34, p < 0.05; r = 0.37, p < 0.05). Levels of sIL-2 were proportional to LV end-diastolic diameter (r = 0.49, p < 0.001) and LV end-systolic diameter (r = 0.58, p < 0.001). Number of cytokines with circulating values above upper level of normal was significantly correlated with Killip class and LVEF (r = 0.40, r = -0.38, p < 0.05). sIL-2r, IL-6, and IL-8 are increased in patients with ACS and systolic dysfunction or AHF. These data suggest that inflammatory cytokine activity detectable in peripheral blood may be useful in identifying subjects with a worse clinical course.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Female; Heart Failure; Humans; Interleukin-2; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Pulmonary Edema; Receptors, Interleukin-2; Ventricular Dysfunction, Left

Acute coronary syndrome (ACS) is one of the most common forms of heart disease. Recent studies have shown that interleukin (IL)-8 plays a key role in the development of atherosclerotic plaques, but the relationship between the common genetic variants of IL-8 and ACS has not been extensively studied.. This case-control study in the Chinese Han population included 675 patients with ACS and 636 age- and sex-matched controls. We investigated IL-8 polymorphisms and their association with susceptibility to ACS. The investigation was replicated in the second study comprising 360 cases and 360 control subjects. The plasma concentration of IL-8 was measured by enzyme-linked immunosorbent assay.. IL-8 -251 A/T polymorphism was associated with increased susceptibility to ACS (P=0.004; odds ratio=1.30; 95% confidence interval: 1.12-1.53). The second study yielded similar results. An increased IL-8 level was found in the plasma of acute myocardial infarction patients, suggesting that IL-8 -251 A/T may affect the expression of IL-8.. IL-8 -251 A/T polymorphism is associated with ACS risk in the Chinese Han population and the A allele of IL-8 -251 A/T may be an independent predictive factor for ACS.

Topics: Acute Coronary Syndrome; Aged; Base Sequence; Case-Control Studies; China; DNA Primers; Ethnicity; Female; Humans; Interleukin-8; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide

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

Studies have shown that erythrocyte membranes are present within necrotic cores in atherosclerotic plaques, and that circulating erythrocytes in patients with acute coronary syndrome (ACS) have increased total cholesterol content (CEM). Interleukin-8 (IL-8) binds to erythrocytes and during intraplaque haemorrhage it is released into the plaque and thus may contribute to inflammatory cascade and atherosclerotic plaque instability. The present study was undertaken to test the hypothesis that erythrocyte membrane IL-8 is elevated in patients with ACS compared with those with chronic stable angina (CSA).. Consecutive patients who presented with CSA (n = 120, 92 men, 62 +/- 9 years), ACS (n = 118, 90 men, 62 +/- 10 years) or with chest pain who had normal coronary arteries (n = 36, 26 men, 60 +/- 7 years), were studied prospectively. IL-8 concentrations in erythrocyte membranes (rIL-8) and in plasma (pIL-8), C-reactive protein (CRP) and CEM were measured. rIL-8 levels [mean +/- 1 SD (standard deviation)] were higher in ACS (102.9 +/- 70.1 pg/mL) compared with CSA (44.7 +/- 22.8 pg/mL) (P < 0.001). No difference in pIL-8 levels between the two coronary artery disease groups was observed (P = 0.280). Serum CRP levels were correlated with rIL-8 levels (r = 0.294, P < 0.001); no association was found between CRP and pIL-8 levels (r = 0.025, P = 0.706). Further, rIL-8 had an independent association with ACS, when CRP and CEM were taken into consideration.. This study shows for the first time that rIL-8 content was significantly higher in ACS, compared with CSA. These findings endorse results from our previous studies suggesting that erythrocytes may play an important role in the development of unstable atherosclerotic plaque.

Topics: Acute Coronary Syndrome; Angina Pectoris; Biomarkers; Cholesterol; Disease Progression; Erythrocyte Membrane; Erythrocytes; Female; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Predictive Value of Tests; Prospective Studies

Inflammation in acute coronary syndrome (ACS) can identify those at greater long-term risks for heart failure (HF) and death. The present study assessed the performance of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) (cytokines involved in the activation and recruitment of leukocytes) in addition to known biomarkers [e.g., N-terminal pro-brain natriuretic peptide (NT-proBNP)] for predicting HF and death in an ACS population.. In a cohort of 216 ACS patients, NT-proBNP (Elecsys; Roche) and IL-6, IL-8, and MCP-1 (evidence investigator; Randox) were measured in serial specimens collected early after symptom onset (n = 723). We collected at least 2 specimens from each participant: an early specimen (median 2 h; interquartile range 2-4 h) and a later specimen (9 h; 9-9 h), and used the later specimens' biomarker concentrations for risk stratification.. An increase in both IL-6 and NT-proBNP was observed but not for IL-8 or MCP-1 early after pain onset. Kaplan-Meier analysis demonstrated that individuals with increased NT-proBNP (>183 ng/L) or cytokines (IL-6 > 6.4 ng/L; above upper limit of normal for IL-8 or MCP-1) had a greater probability of death or HF in the following 8 years (P <0.05). In a Cox proportional hazard model adjusted for both CRP and troponin I, increased IL-6, MCP-1, and NT-proBNP remained significant risk factors. Combining all 3 biomarkers resulted in a higher likelihood ratio for death or HF than models restricted to any 2 of these biomarkers.. IL-6, MCP-1, and NT-proBNP are independent predictors of long-term risk of death or HF, highlighting the importance of identifying leukocyte activation and recruitment in ACS patients.

Topics: Acute Coronary Syndrome; Aged; Chemokine CCL2; Female; Heart Failure; Humans; Inflammation; Interleukin-6; Interleukin-8; Leukocytes; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Retrospective Studies; Risk Factors