interleukin-8 and Angina-Pectoris

Physical activity is effective in primary and secondary prevention of cardiovascular disease. In this study, we tested the hypothesis that exercise training improves glucose and lipid metabolism, the inflammatory/anti-inflammatory balance, and the outcome of elective percutaneous coronary intervention (PCI) in patients with stable coronary disease.. Sixty-two patients scheduled to undergo PCI for stable angina were randomized to intensive physical activity (n=33) consisting of home-based exercise on a bicycle ergometer or maintain their usual sedentary life (n=29). The training program started 2 months before PCI and terminated 6 months afterwards. Clinical examination, blood sampling (fasting glucose, glycated hemoglobin, lipid profile, apolipoprotein B, apolipoprotein A1, C-reactive protein, serum amyloid A, interleukin-6, interleukin-8, and interleukin-10), and maximal exercise tests were performed at inclusion, 1 week before PCI, and 3 and 6 months afterwards.. Fifty-six patients [28 per group, 45 men, mean age 63 (SD 7.8) years] completed the follow-up. According to self-reports, patients in the training group exercised more often and longer [4.9 (SD 1.1) vs. 0.6 (SD 1.3) days/week, 36 (SD 12) vs. 15 (SD 31) min/session, P<0.0001]. Improvement in maximal exercise capacity was significantly better in the training group [27 (SD 27) vs. 9 (SD 27) W, P=0.02]. Exercise had no significant effects on glucose and lipid metabolism, plasma cytokines, or acute-phase reactants.. A home-based training program significantly improved maximal exercise capacity but did not affect glucose or lipid metabolism or markers of inflammation.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Apolipoprotein A-I; Apolipoproteins B; Biomarkers; Blood Glucose; C-Reactive Protein; Coronary Disease; Energy Metabolism; Exercise Therapy; Exercise Tolerance; Female; Glycated Hemoglobin; Home Care Services; Humans; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Lipids; Male; Middle Aged; Serum Amyloid A Protein; Sweden; Time Factors; Treatment Outcome

Cardiac inflammatory responses appear to play a pivotal role in scar formation after acute myocardial infarction. Monocyte chemotactic and activating factor (MCAF) monocyte chemoattractant protein-1 (MCP-1) is a cytokine with chemotactic activity for mononuclear phagocytes, but also for NK cells, T cells, mast cells, and basophils. To investigate the possible involvement of MCAF/MCP-1 in the pathogenesis, its course was studied in patients with acute myocardial infarction. Twenty-three consecutive patients with acute myocardial infarction and 18 patients with angina pectoris were studied. Cytokines were measured by enzyme-linked immunosorbent assay. Plasma levels of interleukin IL-1alpha, IL-1beta, and IL-2 were below the detection limit of our method. IL-6 and interferon-gamma were detected in 17.4%, and tumor necrosis factor-alpha in 13.0% of patients with acute myocardial infarction, but the frequency was not statistically significantly different from that in angina pectoris. The plasma level of MCAF/MCP-1 in myocardial infarction tended to increase at 3 h after the onset of chest pain (133 +/- 19 pg/ml, P= 0.06) and was significantly elevated at 9 h (143 +/- 20 pg/ml) when compared with that in angina pectoris (87 +/- 6 pg/ml, P<0.05). The MCAF/MCP-1 level remained increased during the 24-hours observation period (P<0.01), and maximum level (168 +/- 13 pg/ml) was seen at 24 hour. The level of MCAF/ MCP-1 correlated significantly with the plasma level of another chemokine, IL-8, at 12 h after the onset of chest pain (r=0.51, P<0.05), suggesting that common stimuli mediate the release of both cytokines in myocardial infarction. The identification of MCAF/MCP-1 as an inflammatory mediator in acute myocardial infarction suggests that mononuclear phagocytes may play an important role in the early stage of the disease.

Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Chemokine CCL2; Cytokines; Female; Humans; Interleukin-8; Linear Models; Male; Middle Aged; Myocardial Infarction

Inflammatory cytokines are implicated in the development of atherosclerosis and cardiomyocyte injury during acute myocardial infarction (AMI). This study aimed to investigate the correlation of eight common inflammatory cytokines with major adverse cardiac event (MACE) risk and further establish a prognostic model in AMI patients.. Serum samples of 210 AMI patients and 20 angina pectoris patients were, respectively, collected at admission, to detect tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-17A, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) via enzyme-linked immunosorbent assay.. TNF-α, IL-6, IL-8, IL-17A, VCAM-1, and ICAM-1 were elevated (all p < 0.050); IL-10 (p = 0.009) was declined; IL-1β (p = 0.086) was not varied in AMI patients compared with angina pectoris patients. TNF-α (p = 0.008), IL-17A (p = 0.003), and VCAM-1 (p = 0.014) were elevated in patients with MACE occurrence compared to patients without MACE occurrence; meanwhile, they possessed a relatively good value for identifying MACE risk via receiver-operating characteristic (ROC) analysis. Subsequent multivariate logistic regression analysis revealed that the independent risk factors for MACE contained TNF-α (odds ratio (OR) = 1.038, p < 0.001), IL-1β (OR = 1.705, p = 0.044), IL-17A (OR = 1.021, p = 0.009), history of diabetes mellitus (OR = 4.188, p = 0.013), history of coronary heart disease (OR = 3.287, p = 0.042), and symptom-to-balloon time (OR = 1.064, p = 0.030), whose combination disclosed a satisfying prognostic value for MACE risk (area under the curve: 0.877, 95% CI: 0.817-0.936).. Elevated levels of serum TNF-α, IL-1β, and IL-17A independently correlated with MACE risk in AMI patients, which perhaps provide novel auxiliary for AMI prognostic prediction.

Topics: Angina Pectoris; Cytokines; Humans; Intercellular Adhesion Molecule-1; Interleukin-10; Interleukin-17; Interleukin-1beta; Interleukin-6; Interleukin-8; Myocardial Infarction; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Inflammatory cytokines modulate atherogenesis and plaque rupture to involve in ST-segment elevation myocardial infarction (STEMI) progression. The present study determined eight inflammatory cytokine levels in 212 percutaneous coronary intervention (PCI)-treated STEMI patients, aiming to comprehensively investigate their potency in estimating major adverse cardiac event (MACE) risk.. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-17A, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) of 212 PCI-treated STEMI patients and 30 angina pectoris patients were determined using enzyme-linked immunosorbent assay.. TNF-α (52.5 (43.9-62.6) pg/ml versus 46.4 (39.0-59.1) pg/ml, p = 0.031), IL-8 (61.6 (49.6-81.7) pg/ml versus 46.7 (32.5-63.1) pg/ml, p = 0.001), IL-17A (57.4 (45.7-77.3) pg/ml versus 43.2 (34.2-64.6) pg/ml, p = 0.001), and VCAM-1 (593.6 (503.4-811.4) ng/ml versus 493.8 (390.3-653.7) ng/ml, p = 0.004) levels were elevated in STEMI patients compared to angina pectoris patients, while IL-1β (p = 0.069), IL-6 (p = 0.110), IL-10 (p = 0.052), and ICAM-1 (p = 0.069) were of no difference. Moreover, both IL-17A high (vs. low) (p = 0.026) and VCAM-1 high (vs. low) (p = 0.012) were linked with increased cumulative MACE rate. The multivariable Cox's analysis exhibited that IL-17A high (vs. low) (p = 0.034) and VCAM-1 high (vs. low) (p = 0.014) were independently associated with increased cumulative MACE risk. Additionally, age, diabetes mellitus, C-reactive protein, multivessel disease, stent length, and stent type were also independent factors for cumulative MACE risk.. IL-17A and VCAM-1 high level independently correlate with elevated MACE risk in STEMI patients, implying its potency in identifying patients with poor prognoses.

Topics: Angina Pectoris; Cytokines; Humans; Intercellular Adhesion Molecule-1; Interleukin-10; Interleukin-17; Interleukin-6; Interleukin-8; Percutaneous Coronary Intervention; Prognosis; ST Elevation Myocardial Infarction; Treatment Outcome; Vascular Cell Adhesion Molecule-1

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

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

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

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

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

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

The aims of this study were to investigate the effect of coronary stenting on the release of cytokines and cell-mediated immunity factors and to evaluate the association between inflammation and clinical outcomes at 6 months.. Circulating levels of inflammatory markers and cytokines are elevated in patients with acute coronary syndromes and are related to an unfavorable outcome. The aims of this study were to investigate the effect of coronary stenting on the release of cytokines and cell-mediated immunity factors and to evaluate the association between inflammation and clinical outcomes at 6 months.. Forty patients with single native coronary artery disease treated with stenting were enrolled. Peripheral venous blood samples were collected before and 6 h, 48 h, and 12 weeks after stenting. Serum concentrations of high-sensitivity C-reactive protein, interleukin-6, interleukin-8, tumor necrosis factor-alpha (markers of inflammation) and serum-soluble interleukin-2 receptor for T-lymphocyte activation (sIL2-R, marker of cell-mediated immunity) were measured. Patients also were evaluated clinically one, 3, and 6 months post-stenting or when they presented with cardiovascular symptoms to identify major adverse cardiac events (cardiac death, MI, revascularization).. Concentrations of interleukins 6 and 8 and tumor necrosis factor-alpha peaked at 6 h (11.0, 12.6, and 5.3 pg/ml, respectively). The peak level of high-sensitivity C-reactive protein (2.77 mg/dL) occurred 48 h post stenting, while sIL2-R peaked (495 U/ml) at 12 weeks. Patients who experienced restenosis had higher levels of C-reactive protein at 48 h (4.94 vs. 1.84 mg/dl; P = 0.043) and of IL-8 at 6 h (26.75 vs. 13.55 pg/mL; P = 0.048) than those without restenosis.. Proinflammatory cytokines and inflammatory markers are released into the peripheral circulation early after coronary stenting, and increased levels of some are associated with clinically relevant restenosis.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Biomarkers; Blood Vessel Prosthesis Implantation; C-Reactive Protein; Controlled Clinical Trials as Topic; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Cytokines; Female; Follow-Up Studies; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Receptors, Interleukin-2; Research Design; Stents; Time Factors; Treatment Outcome; Troponin I; Tumor Necrosis Factor-alpha

Membrane-activated complex 1 (Mac-1; CD11b/CD18) is a beta(2) integrin implicated in the pathophysiology of neutrophil-mediated tissue injury whose functional capacity is determined by stimulus-induced conformational activation rather than up-regulation. Mac-1 up-regulation and conformational activation, together with shedding of L-selectin, are reported after in vitro neutrophil activation. However, their regulation on circulating human neutrophils during acute inflammation is unclear. Using flow cytometry, we investigated neutrophil expression of Mac-1, its activation-reporter neo-epitope CBRM1/5, and L-selectin during the inflammatory stimulus of cardiac surgery. A subpopulation of circulating neutrophils expressed CBRM1/5 (CBRM1/5+) under basal conditions (6.28+/-2.59%) and was persistently expanded (9.95+/-4.0%-15.2+/-4.2%; P<0.0001) peri-operatively, whereas total CD11b expression increased only transiently, intra-operatively. L-selectin expression was unchanged on CBRM1/5+ neutrophils, and soluble L-selectin levels decreased intra-operatively (P<0.01), indicating that L-selectin was not shed. Increased CBRM1/5 expression without L-selectin loss or CD11b up-regulation was replicated in vitro by neutrophil stimulation with IL-8, C3a, and platelet-activating factor. Heparin, a known CD11b ligand, which is administered during cardiac surgery, markedly reduced neutrophil expression of conformationally active CD11b in vivo and in vitro, identifying a potential mechanism for its anti-inflammatory properties. We conclude that conformational activation of CD11b occurs on circulating neutrophils in vivo and can occur in the absence of CD11b up-regulation and L-selectin shedding.

Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; CD11b Antigen; Chronic Disease; Complement C3a; Coronary Artery Bypass; Epitopes; Female; Flow Cytometry; Heparin; Humans; Interleukin-8; L-Selectin; Macrophage-1 Antigen; Male; Middle Aged; Neutrophil Activation; Neutrophils; Platelet Activating Factor; Prospective Studies; Protein Conformation; Signal Transduction

Release of progenitor cells is observed during inflammatory conditions and contributes to neovascularization. We, therefore, sought to investigate the relationship of circulating progenitor cells and interleukin (IL)-8 in acute myocardial infarction (AMI).. From patients with stable angina and AMI, serial venous blood samples were obtained. The number of circulating CD133+CD45- progenitor cells, endothelial progenitor cells (EPCs), and circulating endothelial P1H12+CD45- cells was analyzed by flow cytometry. After stenting in patients with AMI, an increase in plasma IL-8 and vascular endothelial growth factor (VEGF) concentrations was observed, which was only minimal in patients with stable angina. Only in patients with AMI, this was followed by an increase in circulating CD133+CD45- progenitor cells. In contrast, circulating endothelial P1H12+CD45- cells and E-selectin RNA expression in peripheral blood were only elevated early in AMI, indicating shedding of activated endothelial cells. Multivariable analysis revealed an association of IL-8 and circulating CD133+CD45- progenitor cells in AMI, in addition to statin therapy and risk factor profile.. In AMI, IL-8 is associated with circulating progenitor cells. In addition to the pro-angiogenic functions of IL-8 and VEGF, this mechanism may contribute to new vessel generation and, thereby, improve myocardial function.

Topics: AC133 Antigen; Angina Pectoris; Antigens, CD; Endothelial Cells; Flow Cytometry; Glycoproteins; Humans; Interleukin-8; Myocardial Infarction; Peptides; Stem Cells; Vascular Endothelial Growth Factor A

In acute myocardial infarction (AMI), proinflammatory plasma C-reactive protein values are strongly associated with postinfarction morbidity and mortality. So far, the cause of these inflammatory changes is not well understood. Therefore, we sought to investigate the relationship between the activation of coagulation and subsequent systemic inflammatory changes in AMI.. Factor Xa (FXa) bound to tissue factor pathway inhibitor and prothrombin fragments F1+2 (F1+2) were used as a measure for activated coagulation. To assess systemic inflammatory changes, plasma interleukin (IL)-6 and IL-8 concentrations were analyzed by immunoassay. Blood samples were taken from 21 patients with AMI and 20 patients with stable angina pectoris. In AMI, tissue factor pathway inhibitor FXa but not F1+2 plasma levels were associated with circulating IL-8 (P=0.01). In vitro experiments revealed that FXa stimulated IL-8 and monocyte chemoattractant protein-1 release and RNA expression in endothelial cells and mononuclear leukocytes by activation of protease-activated receptor-1.. Our data suggest that coagulation FXa may contribute to proinflammatory changes in AMI by stimulation of IL-8 release. Therapeutic inhibition of the proinflammatory effects of FXa may improve the clinical course in AMI. This study investigates the relationship between the activation of coagulation and systemic inflammatory changes in acute myocardial infarction. Tissue factor pathway inhibitor factor Xa but not F1+2 plasma levels were associated with circulating interleukin-8. In vitro factor Xa stimulated interleukin-8 and monocyte chemoattractant protein-1 release and RNA expression by activation of protease-activated receptor 1 as an underlying mechanism.

Topics: Adult; Aged; Angina Pectoris; Cells, Cultured; Chemokine CCL2; Endothelial Cells; Endothelium, Vascular; Factor Xa; Factor Xa Inhibitors; Female; Hirudins; Humans; Inflammation; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Lipoproteins; Male; Middle Aged; Myocardial Infarction; Oligopeptides; Peptide Fragments; Prothrombin; Recombinant Proteins; Umbilical Veins

In this study the effect of a specific glycoprotein IIb/IIIa inhibitor, tirofiban [which also has antiplatelet activity on acute systemic inflammatory responses (IR) during elective percutaneous coronary intervention (PCI)] was evaluated.. Patients with stable angina pectoris and similar baseline characteristics who angiographically had a single lesion in their coronary arteries with a PCI performed on that lesion were enrolled in the study. One group of patients (control group, n = 52) received 0.9% NaCl (15 mL/h for 24 h) and the other group (tirofiban group, n = 55) had tirofiban (10 microg/kg bolus infusion in 3 min and 0.15 microg/kg/min for 24 h) in addition to stenting without pre-dilatation. The effect of interventional procedure on levels of cardiac troponin T (cTnT) and several parameters of acute IR (leukocytes, fibrinogen, C-reactive protein, interleukin-1, interleukin-6, interleukin-8 and tumor necrotizing factor-alpha) was assessed on blood samples obtained from all patients before PCI and at pre-specified time points after PCI.. During the follow-up after PCI, the number of patients becoming cTnT-positive (> 0.1 ng/mL) was greater in the control group [12 (23%) patients vs. 3 (5%) patients, p = 0.01]. However, both groups had changes (generally observed as elevations) in their levels of all inflammatory parameters during the study and C-reactive protein, interleukin-6 and tumor necrotizing factor-alpha levels were elevated significantly. Yet, no significant difference occurred between groups due to these changes in any phase of the study (p > 0.05).. Based on the findings of this study, it was concluded that although tirofiban limits development of myocardial necrosis during elective PCI, it does not directly affect the acute systemic inflammatory responses.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon; C-Reactive Protein; Coronary Angiography; Female; Fibrinogen; Follow-Up Studies; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Middle Aged; Myocardium; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Stents; Tirofiban; Troponin; Tumor Necrosis Factor-alpha; Tyrosine

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

Operations coupled with cardiopulmonary bypass may provoke a systemic inflammatory response, and it has been suggested that this responses causes capillary leakage of proteins, edema formation, and even organ failure. However, capillary leak syndrome is mainly a clinical diagnosis and has not been verified as yet by actual demonstration of protein leakage from the circulation. We have therefore measured the disappearance of labeled plasma protein before and after cardiopulmonary bypass.. Sixteen patients scheduled for elective coronary artery bypass grafting were enrolled in a prospective controlled study. The cardiopulmonary bypass circuit was primed with crystalloids only. Tumor necrosis factor alpha, interleukin 6, interleukin 8, anaphylatoxin C3a, and terminal complement complex C5b9 levels were determined before, during, and 3 hours after cardiopulmonary bypass. The transvascular escape rate of plasma protein from the intravascular compartment was assessed by measuring the disappearance of intravenously injected Evans blue dye before and during the third hour after cardiopulmonary bypass.. A significant inflammatory response could be demonstrated by means of the 5 measured mediators after bypass. The maximal increase, as compared with the baseline value, was found for interleukin 6 (36-fold). The transvascular escape rate of Evans blue dye was similar before and after bypass (7.6 +/- 0.6%/h vs 7.3 +/- 0.6%/h).. The above data confirm the systemic inflammatory response induced by cardiopulmonary bypass. Contrary to expectations, the transvascular escape rate of Evans blue dye did not change when comparing values before and after bypass. The data do not support the concept of increased protein leakage in the exchange vessels after bypass. We were unable to demonstrate a capillary leak syndrome.

Topics: Aged; Angina Pectoris; Capillary Leak Syndrome; Cardiopulmonary Bypass; Combined Modality Therapy; Complement C3a; Complement Membrane Attack Complex; Coronary Artery Bypass; Female; Hemodynamics; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Osmotic Pressure; Postoperative Care; Postoperative Complications; Preoperative Care; Prospective Studies; Treatment Outcome; Tumor Necrosis Factor-alpha

Increasing evidence has indicated the important roles of inflammation and immune response in the development of atherosclerosis and ischemic heart disease (IHD). We measured the serum interleukin (IL)-8 and IL-12 levels of patients with unstable angina pectoris (UAP) and patients with acute myocardial infarction (AMI), and compared findings with those of normal subjects. The results showed that the serum level of IL-8 was significantly higher in patients with UAP and patients with AMI than in healthy control subjects. To our knowledge, this is the first report that serum IL-12 level was elevated in patients with AMI but not in patients with UAP. These findings suggest that IL-8 and IL-12 are involved in the process of IHD, and serum IL-12 may be a marker for differentiating AMI from UAP.

Topics: Aged; Angina Pectoris; China; Female; Humans; Interleukin-12; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Reference Values

To quantify interleukin-8 (IL-8), interleukin-2 (IL-2) and soluble receptor of IL-2 (sIL-2r) in blood serum of patients with various forms of ischemic heart disease (IHD).. Levels of IL-8, IL-2 and sIL-2r were measured with enzyme immunoassay (EIA) in the serum of 75 patients with IHD: angina of effort (group 1), progressive angina (group 2) and acute myocardial infarction (group 3). The EIAs were performed at admission and 2 weeks later.. Baseline levels of IL-2 in group 1 and 2 patients were close (9.1 +/- 1.6 and 10.1 +/- 3.8 pg/ml) being significantly lower in group 3 (0.81 +/- 0.57 pg/ml, p < 0.01). 14 days of therapy did not change the values noticeably. IL-8 level was the highest in group 1 (94.2 +/- 27.6, 20.03 +/- 7.4, 22.47 +/- 4.8 pg/ml, respectively). sIL-2r in the three groups did not vary greatly (73.95 +/- 12.23, 89.46 +/- 18.17, 89.2 +/- 14.17 pg/ml, respectively). SIL-2r levels rose in 2 weeks in group 3 (to 147.67 +/- 18.17 pg/ml).. It is confirmed that IL-2, IL-8 and sIL-2r take part in pathogenesis of IHD. IL-2 and IL-8 levels are persistently high in anginal patients while in patients with acute myocardial infarction they are low. Low concentrations of IL-2 in the latter may be attributed to high levels of its soluble receptor.

Topics: Aged; Angina Pectoris; Female; Humans; Interleukin-2; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Receptors, Interleukin-2; Solubility

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

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Biomarkers; Endothelium, Vascular; Humans; Interleukin-6; Interleukin-8; Time Factors; von Willebrand Factor