Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The initial step in atherosclerosis is the rapid targeting of monocytes to the sites of inflammation and endothelial injury. Serum levels of intercellular adhesion molecule-1 were found to be increased in ischaemic heart disease patients and polymorphisms in the E-selectin gene were associated with accelerated atherosclerosis in young (age < 40 years) patients, further suggesting a role of inflammation in atherosclerosis. Cholesterol loading in macrophages was found to induce interleukin-8 expression, suggesting an association between foam cell formation and beta 2-integrin-dependent adhesion of leukocytes. Enhanced endothelium-platelet interaction induced by hypercholesterolaemia is mediated by von Willebrand factor, whereas platelet adhesion to subendothelial matrix is mediated by fibulin-fibrinogen complexes. Activated platelets mediate the homing of leukocytes by interaction with the subendothelial matrix under shear stresses that do not allow neutrophil adhesion. They may also contribute to the oxidative modification of LDL, provide a source of lipids for foam cell generation and contribute to smooth muscle cell proliferation. Oxidized LDL induces tissue factor in macrophages that also provide sites for fibrin polymerization and decreases the anticoagulant activity of endothelium by interfering with thrombomodulin expression and inactivating tissue factor pathway inhibitor. Intravascular fibrinolysis induced by tissue-type plasminogen activator or urokinase may contribute to the initiation of atherosclerosis by inducing P-selectin and platelet activating factor as well as to plaque rupture, either directly or indirectly, by activating metalloproteinases. Plasminogen activator inhibitor-1 inhibits smooth muscle cell migration and, in the presence of vitronectin, promotes the clearance of thrombin by LDL receptor-related protein at sites of endothelial injury.
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PMID:Thrombosis and atherosclerosis. 933 57

Myocardial ischemia leads to the activation of neutrophils as well as endothelial cells. The interaction between these cells is dependent on certain adhesion glycoproteins which are expressed on their surface. Adhesion of neutrophils to endothelium, mediated by adhesion molecules, has been shown to result in coronary capillary plugging and impairment of coronary blood flow. In certain conditions, upon cell activation, adhesion proteins may be released in soluble form into the circulating blood. The purpose of our study was to verify whether myocardial ischemia occurring during angina episodes results in the release of the soluble adhesion molecules, L-selectin, E-selectin, and intracellular adhesion molecule-1 (ICAM-1), into the circulation. Plasma samples were collected by venepuncture from 15 patients admitted to the emergency room with chest pain caused by attacks of angina pectoris and 15 patients with noncardiac chest pain. To confirm the diagnosis, all patients underwent an exercise stress test and, if not conclusive, 99mTc MIBI SPECT or coronary arteriography. Another set of plasma samples were taken from each patient in the absence of chest pain. In addition, blood for analysis was obtained from 15 sex-and age-matched healthy subjects. Soluble adhesion molecules plasma levels were measured by standard enzyme-linked immunosorbent assay. In patients with angina pectoris, plasma levels of soluble L-selectin estimated during chest pain were significantly higher than in the control group and decreased in the absence of chest pain. Similarly, the mean concentration of soluble ICAM-1 at the time of angina onset was significantly elevated in the patients in comparison with the control group and remained higher, although not significantly, in the absence of chest pain. In patients with noncardiac chest pain, plasma levels of soluble L-selectin did not differ significantly from those observed in control subjects. In this group of patients, the plasma levels of soluble ICAM-1 estimated during pain onset and in the absence of this symptom were not significantly elevated. On the contrary, the mean values of soluble E-selectin in the patients with ischemic cardiac pain during chest pain and in the absence of this symptom, as well as those in the patients with noncardiac chest pain during or without symptoms, remained unchanged in comparison with the control group. During attacks of angina pectoris an increase in the plasma levels of the soluble adhesion molecules, ICAM-1 and L-selectin, was noted, possibly reflecting activation of neutrophils and endothelial cells during myocardial ischemia. However, E-selectin plasma levels remained unchanged in response to myocardial ischemia.
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PMID:Increased release of the soluble form of the adhesion molecules L-selectin and ICAM-1 but not E-selectin during attacks of angina pectoris. 1044

We report the case of a 34-year-old female patient who died 4 days after hospital admission of acute heart failure clinically mimicking ischemic heart disease. Microscopic examination of the heart showed severe myocarditis. Polymerase chain reaction (PCR), including quantitative real-time PCR, disclosed exclusively parvovirus B19 (PVB19), with a high viral load of 4.3x10(5) PVB19 viral genome equivalents per microg myocardial nucleic acid. Radioactive in situ hybridization detected viral genomes in endothelial cells (ECs) predominantly in the venular compartment and (to a lesser degree) in small arteries and arterioles of the heart, but not in cardiac myocytes or other tissue components. Concomitant with EC infection, marked expression of the adhesion molecule E-selectin was noted, accompanied by margination, adherence, penetration, and perivascular infiltration of T lymphocytes. We speculate that, due to the high viral load in cardiac ECs, PVB19 infection of endothelial cells was sufficient to induce impaired coronary microcirculation with secondary cardiac myocyte necrosis.
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PMID:Fatal parvovirus B19-associated myocarditis clinically mimicking ischemic heart disease: an endothelial cell-mediated disease. 1260 72

Ischemia and reperfusion of the myocardium initiate an inflammatory response directed against the myocardium, and many studies attribute a significant portion of this injury to leukocytes. Leukocyte and endothelial cell adhesion molecules are responsible for neutrophil-endothelial cell interactions in coronary vasculature following ischemia and reperfusion. Interactions between beta(2)-integrins and intercellular adhesion molecule-1 are responsible for firm adhesion of neutrophils to the coronary endothelium in acute cardiac inflammation. Leukocyte-expressed CD18 plays a crucial role, and genetic deficiency of CD18 significantly attenuates myocardial ischemia-reperfusion injury. Genetic deficiency of intercellular adhesion molecule-1 also minimizes myocardial necrosis following ischemia and reperfusion. The selectin family of adhesion glycoproteins also participates in various phases of leukocyte-endothelial interactions, and studies with P-selectin- and E-selectin-deficient mice have shown attenuation of both neutrophil accumulation and myocardial injury following myocardial ischemia and reperfusion.
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PMID:Leukocyte and endothelial adhesion molecule studies in knockout mice. 1506 59

The capsular polysaccharide glucuronoxylomannan (GXM) of Cryptococcus neoformans has been shown to interfere with neutrophil migration. Although several receptors have been implied to mediate this process, the structural perspectives are unknown. Here, we assess the contribution of 6-O-acetylation and xylose substitution of the (1-->3)-alpha-d-mannan backbone of GXM, the variable structural features of GXM, to the interference with neutrophil migration. We compare chemically deacetylated GXM and acetyl- or xylose-deficient GXM from genetically modified strains with wild-type GXM in their ability to inhibit the different phases of neutrophil migration. Additionally, we verify the effects of de-O-acetylation on neutrophil migration in vivo. De-O-acetylation caused a dramatic reduction of the inhibitory capacity of GXM in the in vitro assays for neutrophil chemokinesis, rolling on E-selectin and firm adhesion to endothelium. Genetic removal of xylose only marginally reduced the ability of GXM to reduce firm adhesion. In vivo, chemical deacetylation of GXM significantly reduced its ability to interfere with neutrophil recruitment in a model of myocardial ischemia (65% reduction vs a nonsignificant reduction in tissue myeloperoxidase, respectively). Our findings indicate that 6-O-acetylated mannose of GXM is a crucial motive for the inhibition of neutrophil recruitment.
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PMID:O-acetylation of cryptococcal capsular glucuronoxylomannan is essential for interference with neutrophil migration. 1558 78

During myocardial reperfusion injury, oxidative stress induces DNA damage and activation of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1), resulting in cardiovascular dysfunction. In this study, we investigated the biological effects and the molecular mechanisms of two structurally unrelated selective inhibitors of PARP-1, 3-aminobenzamide (3-AB) and 1,5-dihydroxyisoquinoline (-DIQ), in an in vivo model of myocardial ischemia and reperfusion. Male Wistar rats were subjected to 30 min of occlusion followed by reperfusion (up to 24 h) of the left anterior descending coronary artery. In vehicle-treated rats, ischemia and reperfusion induced extensive myocardial damage and marked neutrophil infiltration (as indicated by myeloperoxidase activity). Caspase 3 was maximally activated within 15 to 30 min after reperfusion, suggesting the occurrence of apoptosis. These inflammatory events were associated with activation of the transcription factor activator protein-1 (AP-1) in the reperfused hearts. Treatment of the rats with the PARP-1 inhibitors, 3-AB or 1,5-DIQ, reduced myocardial damage, neutrophil infiltration, and caspase activation. This cardioprotection was associated with reduction of AP-1 activation. Furthermore, in in vitro cytokine-stimulated human endothelial cells, expression of intercellular adhesion molecule 1, vascular cellular adhesion molecule 1, and P- and E-selectin was significantly reduced by treatment with 3-AB or 1,5-DIQ. On the contrary, in vivo or in vitro treatment with nicotinic acid, a chemical analogue of PARP inhibitors, which lacks the ability to inhibit the catalytic activity of PARP-1, was unable to afford any protective effect and to prevent activation of AP-1. Our data demonstrate that inhibition of catalytic activity of PARP-1 may provide cardioprotection by regulating stress-induced signal transduction pathways.
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PMID:Inhibitors of poly (ADP-ribose) polymerase ameliorate myocardial reperfusion injury by modulation of activator protein-1 and neutrophil infiltration. 1571 20

Inflammation and leukocyte activation/infiltration play a major role in the initiation and progression of cardiovascular diseases including atherosclerosis and heart failure. Acute p38 mitogen-activated protein kinase (MAPK) pathway inhibition attenuates tissue damage and leukocyte accumulation in myocardial ischemia/reperfusion injury, although its effect on the acute phase of leukocyte recruitment has not been elucidated. The purpose of this study was to test the hypothesis that acute treatment of rats with a selective p38 inhibitor, SB-239063, inhibits ischemia/reperfusion-induced leukocyte-endothelial adhesion in vivo. Male Sprague-Dawley rats were treated with either SB-239063 (10 mgkg(-1)), dexamethasone (3 mgkg(-1)) or vehicle 1h prior to ischemia. Postcapillary venules were observed microscopically in exteriorized, superfused cremaster tissue. Leukocytes were fluorescently labeled in vivo using intravenous rhodamine 6G. Leukocyte adhesion, rolling, and rolling velocities were quantitated prior to 30 min ischemia, and at several time points during a 90 min reperfusion period. Ischemia caused a 3-fold increase in adherent leukocytes 5 min following reperfusion, a response that was maintained throughout the monitoring period (90 min) in vehicle-treated animals. SB-239063, at a dose known to inhibit p38 MAPK activity in vivo (10 mgkg(-1)), had no effect on ischemia/reperfusion-induced leukocyte adhesion, the number of rolling leukocytes, rolling velocities during the reperfusion period or adhesion molecule expression (P-, E-selectin, VCAM-1, ICAM-1). In contrast, dexamethasone completely blocked leukocyte adhesion in response to ischemia/reperfusion, and reduced expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). We conclude that p38 MAPK may not play a role in initial leukocyte recruitment in response to ischemia/reperfusion injury, but could affect leukocyte emigration, thereby resulting in increased leukocyte accumulation in ischemic-reperfused tissue.
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PMID:Role of p38 MAP kinase in postcapillary venule leukocyte adhesion induced by ischemia/reperfusion injury. 1574 61

We demonstrated previously that thrombin stimulation of human coronary artery endothelial cells (HCAEC) results in release of choline lysophospholipids [lysophosphatidylcholine (lysoPtdCho) and lysoplasmenylcholine (lysoPlsCho)]. These amphiphilic metabolites have been implicated in arrhythmogenesis following the onset of myocardial ischemia, but studies examining their direct effects on the vasculature remain limited. We and others have shown that thrombin and lysoPtdCho can increase cell surface adhesion molecules and adherence of circulating inflammatory cells to the endothelium. This study supports our hypothesis that these changes may be mediated, at least in part, by lysoPlsCho, thus implicating this metabolite as an inflammatory mediator in the coronary vasculature and a modulator of the progression of atherosclerosis. Apical stimulation of HCAEC with thrombin resulted in the production and release of choline lysophospholipids from the apical surface of the HCAEC monolayer. Basolateral stimulation had no effect on choline lysophospholipid production or release from either the apical or basolateral surface of the HCAEC monolayer. Incubation of HCAEC with lysoPlsCho or lysoPtdCho resulted in similar increases in HCAEC surface expression of P-selectin and E-selectin. Furthermore, lysoPlsCho increased cell surface expression of P-selectin, E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 with a time course similar to that of thrombin stimulation. Increased presence of cell surface adhesion molecules may contribute to the significant increase in adherence of neutrophils to either thrombin- or lysoPlsCho-stimulated HCAEC. These results demonstrate that the presence of thrombin at sites of vascular injury in the coronary circulation, resulting in increased choline lysophospholipid release from the HCAEC apical surface, has the potential to propagate vascular inflammation by upregulation of adhesion molecules and recruitment of circulating inflammatory cells to the endothelium.
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PMID:Lysoplasmenylcholine increases neutrophil adherence to human coronary artery endothelial cells. 1772 94

Cardiovascular diseases are influenced by inheritance and environmental factors. There is a growing number of genetic variants, which may be included in the genesis and development of coronary artery disease (CAD). CAD or ischemic heart disease is a set of clinical symptoms caused by inadequate transport of oxygen because of changes in coronary circulation leading to myocardial ischemia. The most common cause of CAD is atherosclerosis of coronary arteries, which primarily narrows or occludes the lumen of coronary arteries or stimulates thrombosis. In this review, the role of the most important polymorphisms in adhesion molecules, intracellular adhesion molecule-1, integrins alpha2beta1 and beta3, E-selectin as well as of inflammation mediators, tumor necrosis factors alpha and beta, in the development of CAD risk and myocardial infarction is discussed. A review of different genotyping results provides an insight into the mechanisms responsible for the disease risk and helps detect the key sets of predictive markers that are clinically informative.
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PMID:[Influence of gene polymorphisms in adhesion molecules and inflammation mediators as risk factors for coronary heart disease and myocardial infarction--an overview]. 1836 99

The aim of the study was assessment of plasma level of ceramides and adhesive molecules in patients with stable ischaemic heart disease (IHD). Ischaemic heart disease was verified by coronary angiography as a 1.2 or 3 vessels disease. The study based on 35 patients (11F, 24 M,aged 40-74 yrs). The control group consisted of 16 healthy persons (5F, 11M, aged 43-66 yrs). Fasting plasma was drown to asses levels of ceramides, the soluble forms of E-selectin and intercellular adhesive molecule-1 (ICAM-1) and total cholesterol, chol-HDL, chol-LDL and triglicerides. Decreased concentrations of ceramides with mono- and polyunsaturated fatty acids were observed in patients with stable IHD. In 3 vessels disease the total level of ceramides was higher than in 1 vessel disease (p < 0.05). The plasma concentration of sE-selectin, ssICAM-1 were elevated in patients compared to control group (p < 0.02 and p < 0.05, respectively). The plasma levels of sICAM-1 were significantly higher in 3 vessels disease than in 1 vessel disease (p < 0.01). Ceramides concentration with saturated fatty acids correlated with adhesive molecules (p < 0.05). A negative correlation was observed between sICAM-1 concentration and ceramides with palmitoleic acid or docosahexaenoic acid (p < 0.05).
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PMID:[Ceramides and adhesive molecules in stable ischaemic heart disease]. 1862 21


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