UMLS:C0151744 - FACTA Search

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Query: UMLS:C0151744 (myocardial ischemia)
31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiopathic dilated cardiomyopathy (DCM) is characterised by a severe dysfunction of the heart muscle resulting in terminal heart failure. Its pathogenesis is believed to be multifactorial involving genetic predisposition, viral infection and autoimmunity, but little is known in detail, and there is no curative treatment except transplantation. Interleukin-1 (IL-1) mediates inflammatory responses to infection and injury. It can be produced by several widely-distributed cell types, including macrophages, and is thought to depress myocyte contractility by stimulating nitric oxide synthase. To investigate whether this pro-inflammatory cytokine may be a pathogenic mediator in DCM, IL-1beta mRNA and protein were evaluated in coronary arteries and myocardium from patients undergoing cardiac transplantation for DCM.IL-1beta mRNA was detected by PCR of cDNA and northern blots of mRNA in coronary arteries and myocardium from patients with DCM. By comparison, samples from patients with ischaemic heart disease (IHD) contained much less IL-1beta mRNA. In contrast, mRNA for other cytokines (TNFalpha, IL-6, IL-10, PDGFA) were similar in both pathologies. In DCM, IL-1beta mRNA and protein were localised to infiltrating macrophages in interstitial regions between myocytes, some of the myocytes themselves, and endothelial cells of vessels in the wall of the arteries. These results suggest that local production of the pro-inflammatory cytokine, IL-1beta may play a part in the pathogenesis of DCM.
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PMID:Interleukin-1 in myocardium and coronary arteries of patients with dilated cardiomyopathy. 951 98

The purpose of this study was to assess lymphocyte receptors expression in patients with ischemic heart diseases, as well as to measure the plasma levels of interleukin (IL) 2, 6 and 10. T Lymphocytes are found in large numbers in human atherosclerotic plaques, indicating that immune and inflammatory mechanisms are important factors in the pathogenesis of atherosclerosis. Recent data have also implicated T lymphocytes in the pathogenetic mechanism of unstable angina and ischemic heart disease. Three groups of patients were studied: 42 with an acute ischemic syndrome (AIS), 36 with stable angina (SA) and 39 healthy controls. To characterize lymphocyte phenotype, flow cytometry was performed in whole-blood samples. IL-2, IL-6 and IL-10 were measured using the ELISA method. Double fluorescence evaluation showed an increase in CD8+/CD11b+ cells (cytotoxic T lymphocytes) and in CD11b+/CD16+CD56+ cells (NK lymphocytes) in the AIS group and in SA group as compared to the control group (P < 0.05 and P < 0.001, respectively). IL-2 was increased in the AIS and SA groups compared to the control group (AIS 4.5 +/- 0.5 pg/ml; SA 6.3 +/- 0.6 pg/ml; controls 2.4 +/- 0.8 pg/ml, P < 0.05), whereas IL-6 was higher in the AIS group than in the other two groups (AIS 10.8 +/- 1.8 pg/ml; SA 1.8 +/- 0.8 pg/ml; controls 1.2 +/- 0.6 pg/ml, P < 0.0001). These data show that patients with ischemic heart disease have an increase in circulating cytotoxic T lymphocytes and in IL-2 plasma levels, irrespective of their clinical presentation, compared to normal control subjects, whereas IL-6 is elevated only in patients with AIS.
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PMID:Plasma levels of interleukin 2, 6, 10 and phenotypic characterization of circulating T lymphocytes in ischemic heart disease. 1048 65

Reperfusion of the ischemic myocardium is associated with a dramatic inflammatory response leading to TNF-alpha release, IL-6 induction, and subsequent neutrophil-mediated cytotoxic injury. Because inflammation is also an important factor in cardiac repair, we hypothesized the presence of components of the inflammatory reaction with a possible role in suppressing acute injury. Thus, we investigated the role of IL-10, an anti-inflammatory cytokine capable of modulating extracellular matrix biosynthesis, following an experimental canine myocardial infarction. Using our canine model of myocardial ischemia and reperfusion, we demonstrated significant up-regulation of IL-10 mRNA and protein in the ischemic and reperfused myocardium. IL-10 expression was first detected at 5 h and peaked following 96-120 h of reperfusion. In contrast, IL-4 and IL-13, also associated with suppression of acute inflammation and macrophage deactivation, were not expressed. In the ischemic canine heart, CD5-positive lymphocytes were the predominant source of IL-10 in the myocardial infarct. In the absence of reperfusion, no significant induction of IL-10 mRNA was noted. In addition, IL-12, a Th1-related cytokine associated with macrophage activation, was not detected in the ischemic myocardium. In vitro experiments demonstrated late postischemic cardiac-lymph-induced tissue inhibitor of metalloproteinases (TIMP)-1 mRNA expression in isolated canine mononuclear cells. This effect was inhibited when the incubation contained a neutralizing Ab to IL-10. Our findings suggest that lymphocytes infiltrating the ischemic and reperfused myocardium express IL-10 and may have a significant role in healing by modulating mononuclear cell phenotype and inducing TIMP-1 expression.
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PMID:IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury. 1094 12

Low rates of coronary heart disease was found in Greenland Eskimos and Japanese who are exposed to a diet rich in fish oil. Suggested mechanisms for this cardio-protective effect focused on the effects of n-3 fatty acids on eicosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction, cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids. One attractive suggestion is a direct cardiac effect of n-3 fatty acids on arrhythmogenesis. N-3 fatty acids can modify Na+ channels by directly binding to the channel proteins and thus, prevent ischemia-induced ventricular fibrillation and sudden cardiac death. Though this is an attractive explanation, there could be other actions as well. N-3 fatty acids can inhibit the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factoralpha (TNFalpha) and interleukin-1 (IL-1) and IL-2 that are released during the early course of ischemic heart disease. These cytokines decrease myocardial contractility and induce myocardial damage, enhance the production of free radicals, which can also suppress myocardial function. Further, n-3 fatty acids can increase parasympathetic tone leading to an increase in heart rate variability and thus, protect the myocardium against ventricular arrhythmias. Increased parasympathetic tone and acetylcholine, the principle vagal neurotransmitter, significantly attenuate the release of TNF, IL-1beta, IL-6 and IL-18. Exercise enhances parasympathetic tone, and the production of anti-inflammatory cytokine IL-10 which may explain the beneficial action of exercise in the prevention of cardiovascular diseases and diabetes mellitus. TNFalpha has neurotoxic actions, where as n-3 fatty acids are potent neuroprotectors and brain is rich in these fatty acids. Based on this, it is suggested that the principle mechanism of cardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNFalpha and IL synthesis and release, modulation of hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increase in acetylcholine release, the vagal neurotransmitter. Thus, there appears to be a close interaction between the central nervous system, endocrine organs, cytokines, exercise, and dietary n-3 fatty acids. This may explain why these fatty acids could be of benefit in the management of conditions such as septicemia and septic shock, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, diabetes mellitus, essential hypertension and atherosclerosis.
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PMID:Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? 1113 72

Inflammatory cytokines have been implicated in myocardial function, severe congestive heart failure and sepsis. The present study tested the hypothesis that cytokine levels are elevated after low-risk coronary artery bypass surgery (CABG), and that they may be associated with postoperative cardiac dysfunction. Twenty male patients undergoing elective CABG in cardiopulmonary bypass (CPB) were studied. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and IL-10 were measured before anesthesia induction, 5 minutes after, and 1, 4, and 20 hours after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were measured postoperatively. Hemodynamic data were also recorded. Myocardial ischemia was followed by an increase in the plasma levels of IL-6, IL-8, and IL-10. The duration of IL-6 response lasted throughout the postoperative period studied. Plasma cytokine levels at 1 hour after reperfusion correlated with the maximum CK-MB value (IL-6, r = 0.587, p < 0.01; IL-8, r = 0.460, p < 0.05; IL-10, r = 0.570, p < 0.05). Higher plasma IL-6 and IL-8 levels after reperfusion tended to be linked with lower cardiac index. The present results confirm that the levels of inflammatory cytokines IL-6, IL-8, and IL-10 are elevated after CABG. Increased systemic pro-inflammatory cytokine levels were partially associated with postoperative myocardial dysfunction. </hea
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PMID:Cytokine Responses in Low-Risk Coronary Artery Bypass Surgery. 1117 83

Interleukin (IL)-12 is a heterodimeric cytokine that is secreted mainly by antigen-presenting cells and plays a key role in determining the nature of immune response to exogenous or endogenous antigens. Negative regulators of IL-12 production include IL-10. With use of wild-type and IL-10-deficient mice, the aim of the current investigation was to determine whether IL-12 is produced in myocardial reperfusion injury and whether endogenous IL-10 modulates its production. IL-10 levels were significantly higher than baseline at both 2 h and 6 h after the start of the reperfusion. In the IL-10-deficient animals, no IL-12 could be detected in the plasma. In the wild-type animals, at baseline, and at 1-6 h after myocardial ischemia-reperfusion, no detectable increases in IL-12 were measured. However, in the IL-10-deficient mice, a significant and pronounced increase in IL-12 was detected. IL-10-deficient mice also exhibited significantly higher mortality during reperfusion than wild-type animals. We conclude that the production of IL-12 in myocardial reperfusion injury is dramatically affected by the levels of endogenous IL-10.
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PMID:Production of interleukin-12 is under the control of endogenous interleukin-10 in myocardial ischemia-reperfusion. 1119 62

Expression of interleukin (IL)-10 influences the frequency of rejection events after organ transplantation. Therefore, 70 heart transplant patients were genotyped for three single nucleotide polymorphisms and a microsatellite polymorphism in the promotor region of the IL-10 gene. The promoter region was amplified by polymerase chain reaction and genotyped by a colorometric oligo ligation assay and gene scan analysis, respectively. Patient groups consisted of patients suffering from dilated cardiomyopathy or ischaemic heart disease. Cardiac donors served as control group. No correlation was found between genotypes and heart failure or rejection after heart transplantation. This may indicate that in heart transplantation, the total balance of cytokine production is more important for post-transplant rejection activities than the levels of IL-10 as such.
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PMID:No association between IL-10 promoter gene polymorphism and heart failure or rejection following cardiac transplantation. 1126 May 10

One of the major therapeutic goals of modern cardiology is to design strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair following myocardial infarction. However, a sound understanding of the biology is necessary before a specific intervention is pursued on a therapeutic basis. This review summarizes our current understanding of the cellular and molecular mechanisms regulating the inflammatory response following myocardial ischemia and reperfusion. Myocardial necrosis induces complement activation and free radical generation, triggering a cytokine cascade initiated by Tumor Necrosis Factor (TNF)-alpha release. If reperfusion of the infarcted area is initiated, it is attended by an intense inflammatory reaction. Interleukin (IL)-8 synthesis and C5a activation have a crucial role in recruiting neutrophils in the ischemic and reperfused myocardium. Neutrophil infiltration is regulated through a complex sequence of molecular steps involving the selectins and the integrins, which mediate leukocyte rolling and adhesion to the endothelium. Marginated neutrophils exert potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. Despite this potential injury, substantial evidence suggests that reperfusion enhances cardiac repair improving patient survival; this effect may be in part related to the inflammatory response. Monocyte Chemoattractant Protein (MCP)-1 is also markedly upregulated in the infarcted myocardium inducing recruitment of mononuclear cells in the injured areas. Monocyte-derived macrophages and mast cells may produce cytokines and growth factors necessary for fibroblast proliferation and neovascularization, leading to effective repair and scar formation. At this stage expression of inhibitory cytokines such as IL-10 may have a role in suppressing the acute inflammatory response and in regulating extracellular matrix metabolism. Fibroblasts in the healing scar undergo phenotypic changes expressing smooth muscle cell markers. Our previous review in this journal focused almost exclusively on reduction of the inflammatory injury. The current update is prompted by the potential therapeutic opportunity that the open vessel offers. By promoting more effective tissue repair, it may be possible to reduce the deleterious remodeling, that is the leading cause of heart failure and death. Elucidating the complex interactions and regulatory mechanisms responsible for cardiac repair may allow us to design effective inflammation-related interventions for the treatment of myocardial infarction.
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PMID:The inflammatory response in myocardial infarction. 1174 11

The role of nitric oxide (NO) generated by the inducible NO synthase (iNOS) during myocardial ischemia and reperfusion is not understood. We investigated the role of iNOS during early reperfusion damage induced in genetically deficient iNOS (iNOS-/-) mice and wild-type littermates. In wild-type mice, ischemia (60 min) and reperfusion (60 min) induced an elevation in serum levels of creatine phosphokinase and myocardial injury characterized by the presence of scattered apoptotic myocytes and mild neutrophil infiltration. Northern blot analysis showed increased expression of iNOS, whose activity was markedly elevated after reperfusion. Immunohistochemistry showed staining for nitrotyrosine; Western blot analysis showed elevated expression of heat shock protein 70 (HSP70), a putative cardioprotective mediator. Plasma levels of nitrite and nitrate, tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and IL-10 were also increased. These events were preceded by degradation of inhibitor kappaBalpha (IkappaBalpha), activation of IkappaB kinase complex (IKK) and c-Jun-NH2-terminal kinase (JNK), and subsequently activation of nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) as early as 15 min after reperfusion. In contrast, iNOS-/- mice experienced 35% mortality after reperfusion. The extensive myocardial injury was associated with marked apoptosis and infiltration of neutrophils whereas expression of HSP70 was less pronounced. Nitrotyrosine formation and plasma levels of nitrite and nitrate were undetectable. TNF-alpha and IL-6 were increased and IL-10 was reduced in earlier stages of reperfusion. Activation of IKK and JNK and binding activity of NF-kappaB and AP-1 were significantly reduced. Thus, we conclude that iNOS plays a beneficial role in modulating the early defensive inflammatory response against reperfusion injury through regulation of signal transduction.
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PMID:Absence of inducible nitric oxide synthase modulates early reperfusion-induced NF-kappaB and AP-1 activation and enhances myocardial damage. 1187 82

Understanding of the pathophysiology of atherosclerosis has changed markedly over the past few decades. It is now widely accepted that inflammation plays a fundamental role in the genesis and development of atherosclerosis. Inflammatory mechanisms also appear to determine clinical presentation and disease outcome. Atherosclerotic lesions have high concentrations of inflammatory cells (T lymphocytes and activated macrophages) as well as an abundance of pro-inflammatory cytokines [interleukin (IL)-1, IL-6, IL-8, interferon-gamma, tumor necrosis factor-alpha, etc.] that modulate local inflammatory responses. These may also alter plaque stability and facilitate the development of acute cardiovascular events. The role of anti-inflammatory cytokines in this context remains to be studied. IL-10 is an anti-inflammatory cytokine synthesised by T-lymphocytes and macrophages and has other anti-inflammatory effects. IL-10 expression within human atherosclerotic plaques has been demonstrated and animal experiments have shown that low levels of IL-10 lead to the development of extensive and unstable atherosclerotic lesions. Currently available evidence suggests a potential protective role for IL-10 in atherosclerosis. This new perspective on coronary disease as a chronic inflammatory process may open new avenues for the management of ischemic heart disease.
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PMID:[Interleukin-10 and coronary disease]. 1211 2

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