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)

Chronic inflammatory cells are key components in the progression of atherosclerotic plaques and restenosis after coronary angioplasty. Adhesion molecules are fundamental in inflammatory processes. Therefore, the distributions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM) were investigated in directional coronary atherectomy specimens obtained from 14 patients, in 6 with acute coronary syndromes (myocardial infarction and unstable angina within 1 month), 6 with old myocardial infarction and 2 with stable effort angina. There were eight primary lesions and six restenotic lesions. Atherectomy tissue fragments were snap frozen and cut into 4 microns thick cryostat sections for immunohistochemical staining by avidin-biotin complex immunoperoxidase techniques using adhesion molecule specific monoclonal antibodies BBIG-I1 (ICAM-1) and BBIG-V1 (VCAM). The cells of lesions were characterized in sequential sections by macrophage marker KP1 (CD68), endothelial marker JC/70A (CD31), and smooth muscle cell marker 1A4 (alpha-smooth muscle actin). Four restenotic lesions that had undergone a prior balloon angioplasty within a few months consisted of intimal proliferation and the other lesions were atherosclerotic plaque. Macrophage-rich areas were seen in the lesions from acute coronary syndromes and/or early restenotic lesions. Expression of ICAM-1 or VCAM was strongly associated with macrophage-rich areas, but VCAM staining was weaker than ICAM-1 except in one restenotic lesion. Macrophages that express ICAM-1 and/or VCAM may be important in the unstable plaques and restenotic lesions related to disease activity of ischemic heart disease.
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PMID:[Immunohistochemical analysis of adhesion molecules in directional coronary atherectomy specimens]. 747 44

Soluble adhesion molecules E-selectin, intercellular adhesion molecule (sICAM) and vascular cell adhesion molecule (sVCAM) were measured alongside von Willebrand factor (vWf) in 40 patients with peripheral vascular disease (PVD), 43 with ischaemic heart disease (IHD) and in equal numbers of age and sex matched asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0008) and in patients with PVD (p = 0.0001) relative to their respective controls but levels did not differ between the two patient groups. Raised sICAM was found in both PVD (p = 0.0003) and IHD (p = 0.0059) compared to their respective controls and was higher in PVD than in IHD (p = 0.0088). In the subjects taken as a whole, there was no correlation between vWf and sICAM. Levels of soluble E-selectin and sVCAM did not differ in patients or controls. These data suggest that soluble ICAM may be useful as an index of endothelial cell activation in clinical manifestations of atherosclerosis.
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PMID:Circulating endothelial cell/leukocyte adhesion molecules in atherosclerosis. 752 83

In this study we have assayed the pathophysiological role of intercellular adhesion molecule (ICAM-1), a cytokine-inducible adhesion molecule, in a model of ischaemia reperfusion in the rat. Anaesthetized rats were subjected to occlusion (1 h) of the left main coronary artery followed by reperfusion (1 h). Sham myocardial ischaemia-reperfusion rats (Sham MI/R) were used as controls. Myocardial ischaemia plus reperfusion in untreated rats decreased survival rate, produced a marked myocardial necrosis, increased serum creatine phosphokinase activity, and cardiac myeloperoxidase activity (a marker enzyme commonly used to assess polymorphonuclear leukocyte accumulation). Furthermore, rats subjected to myocardial ischaemia-reperfusion showed an increased pressure rate index, studied as a quantitative means for assessing myocardial oxygen demand. Treatment with monoclonal anti-rat ICAM-1 (1 mg/kg i.v.), 3 h before occlusion of the left main coronary artery, significantly lowered serum creatine phosphokinase activity, blunted leukocyte accumulation and protected the myocardium from injury subsequent to ischaemia and reperfusion injury. These investigations have revealed that ICAM-1 is a critical adhesion molecule in the pathogenesis of ischaemia-reperfusion injury. In addition these results suggest that the use of monoclonal antibodies raised against ICAM-1 can represent a useful tool for the prevention of ischaemia-reperfusion damage.
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PMID:Antibodies against intercellular adhesion molecule 1 protect against myocardial ischaemia-reperfusion injury in rat. 785 76

Cardiac surgery for congenital heart disease often results in postoperative depression of myocardial function due to myocardial ischemia and stunning. The Boston Circulatory Arrest study indicated that myocardial stunning is also observed postoperatively in the immature heart. Neonates less than 3 months of age (N = 162) experienced cardiac outputs that averaged 20% of baseline values in spite of myocardium protection with Plegisol cardioplegia. In order to minimize the effects of myocardial stunning on the immature heart, we examined the effects of preischemic administration of monoclonal antibodies to leukocyte adhesion molecule CD18 (monoclonal R15.7 [Boehringer-Ingelheim]) on the function of blood perfused neonatal lamb hearts. Heart were arrested for 2 hours with a 15 degrees C K+ cardioplegia solution. Antibody treated hearts (N = 9) had significantly better (p < 0.05) recovery of left ventricular (LV) developed pressure (83.9% +/- 2.2% vs 73.6% +/- 3.0% for controls), LV dP/dt (78.4% +/- 3.3% vs 67.4% +/- 3.4% for controls), coronary blood flow (159.5% +/- 12.2% vs 84.4% +/- 3.5% for controls), and myocardial oxygen consumption (129.8% +/- 16.5% vs 71.2% +/- 6.2% for controls) than controls. In addition, recovery of coronary vascular resistance in response to 10(-6) M acetylcholine was significantly better (p = 0.08) in antibody treated hearts (38.4% +/- 4.3%) than in control hearts (13.4 +/- 12.8%). These results support the notions that leukocyte adherence to the endothelium contributes to reperfusion injury after ischemia and that monoclonal antibodies to CD18 may reduce the effects of myocardial stunning after cardiac surgery.
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PMID:Anti-CD18 attenuates myocardial stunning in the isolated neonatal lamb heart. 809 9

It has been suggested that leukocyte adhesion mechanisms play a key role in experimental myocardial infarction. We have recently shown that E-selectin, an adhesion molecule belonging to the selectin family, is involved in the pathogenesis of experimental myocardial ischemia. We investigated the circulating levels of E-selectin, studied as a marker of endothelial dysfunction, in acute myocardial infarction. Our study was carried out in 60 patients, 20 hospitalized for acute myocardial infarction, 20 suffered from angina pectoris and 20 healthy control subjects. Patients with acute myocardial infarction had increased serum levels of soluble E-selectin (sE-selectin = 255 +/- 12 ng/ml) compared to both patients with angina pectoris (sE-selectin = 51 +/- 14 ng/ml). Thrombolytic therapy with urokinase (1,000,000 IU as an intravenous bolus in 5 min, followed by producing reperfusion and reduced the serum levels of sE-selectin (71 +/- 19 ng/ml). Our results confirm previous experimental data and indicate that adhesion mechanisms supporting leukocyte-endothelium interaction may also be operative in human acute myocardial infarction.
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PMID:Soluble E-selectin levels in acute human myocardial infarction. 865 56

Neutrophils play an important role in myocardial ischemia-reperfusion injury. Neutrophil adhesion to the vascular endothelium is one of the important early mechanisms that lead to reperfusion injury. The leukocyte adhesion molecule, L-selectin, plays a major role in the initial interaction between neutrophils and endothelial cells. Intervention aimed at blocking selectins or their associated ligands can exert cardioprotective effects. The purpose of this study was to examine the role of L-selectin in the initiation of transmembrane signaling and regulation of canine neutrophil responses. Cross-linking of canine neutrophil L-selectin using anti-L-selectin antibody induced a rapid and transient increase in intracellular Ca2+ levels and superoxide anion generation that were dependent on the extent of L-selectin cross-linking. The responses were significantly inhibited by the protein tyrosine kinase inhibitor, genistein. The results demonstrate that ligation of canine neutrophil L-selectin is coupled to intracellular signal transduction pathways and the generation of second messengers, which may independently play important regulatory roles in modulating neutrophil-endothelial cell interactions.
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PMID:L-selectin stimulation of canine neutrophil initiates calcium signal secondary to tyrosine kinase activation. 908 5

Carvedilol is a novel, multiple-action cardiovascular drug that is currently approved in many countries for the treatment of hypertension. The reduction in blood pressure produced by carvedilol results primarily from beta-adrenoceptor blockade and vasodilation, the latter resulting from alpha 1-adrenoceptor blockade. These actions, as well as several of the other activities of carvedilol, are associated with cardioprotection in animal models that occurs to a degree that is greater than that observed with other drugs. The multiple actions of carvedilol may also provide the underlying rationale for the use of the drug in the treatment of coronary artery disease and congestive heart failure. By virtue of being both a beta-blocker and a vasodilator, carvedilol significantly decreases myocardial work by reducing all three components of myocardial oxygen demand, namely, heart rate, contractility, and wall tension. The vasodilatory effects of carvedilol reduce afterload, and the resulting decrease in impedance to left ventricular ejection offsets the negative inotropic effect that would normally result from beta-blockade. As a consequence, stroke volume and cardiac output are maintained or even increased in animals and in patients with congestive heart failure who are treated with carvedilol. Carvedilol and several of its metabolites are potent antioxidants, and this activity may account, in part, for the cardioprotective effects of the drug observed in animal models of acute myocardial ischemia and, in theory, could also serve to protect the myocardium of patients with hypertension, coronary artery disease, and congestive heart failure, in which oxidative stress is now recognized to occur. The antioxidant effects of carvedilol may both inhibit the direct cytotoxic actions of reactive oxygen radicals and prevent oxygen-radical induced activation of transcription factors and genes associated with inflammatory and remodeling processes. Accordingly, carvedilol inhibits the gene expression of the intracellular adhesion molecule-1 (ICAM-1), an adhesion molecule for polymorphonuclear leukocytes, which typically infiltrate the myocardium under conditions of ischemia and may exacerbate ischemic injury. The antioxidant activity of carvedilol has been shown to inhibit the oxidation of low density lipoprotein (LDL) in vitro, thereby preventing the formation of this cytotoxic and atherogenic form of LDL. It follows, therefore, that in animal models of hyperlipidemia, carvedilol attenuates aortic lipid accumulation and decreases the aortic content of monocytes and foam cells, and at the same time it has been shown to preserve endothelial integrity and function. These actions of carvedilol are not shared by other beta-blockers or by other drugs currently used in the management of hypertension, coronary artery disease, or congestive heart failure. The multiple actions of carvedilol may provide the underlying pharmacologic rationale for the use of this drug in the treatment of patients with coronary artery disease or congestive heart failure, and these actions may account, at least in part, for the reduction in mortality produced by carvedilol in clinical trials involving patients with congestive heart failure. Likewise, these actions of carvedilol may also provide protection, beyond that afforded from reduction in blood pressure, against secondary organ damage in hypertensive patients treated with the drug.
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PMID:Pharmacology of carvedilol: rationale for use in hypertension, coronary artery disease, and congestive heart failure. 921 Oct 17

Myocardial injury after ischemia (I) and reperfusion (R) is related to leukocyte activation with subsequent release of cytokines and oxygen-derived free radicals as well as complement activation. In our study, the cardioprotective effects of exogenous C1 esterase inhibitor (C1 INH) were examined in a rat model of myocardial I + R (i.e., 20 min + 24 hr or 48 hr). The C1 INH (10, 50 and 100 U/kg) administered 2 min before reperfusion significantly attenuated myocardial injury after 24 hr of R compared to vehicle treated rats (P < .001). Further, cardiac myeloperoxidase activity (i.e., a marker of PMN [polymorphonuclear leukocyte] accumulation) in the ischemic area was significantly reduced after C1 INH treatment compared to vehicle treated animals (0.81 +/- 0.1, 0.34 +/- 0.13, 0.13 +/- 0.1 vs. 1.44 +/- 0.3 U/100 mg tissue, P < .001). In addition, C1 INH (100 U/kg) significantly attenuated myocardial injury and neutrophil infiltration even after 48 hr of reperfusion compared to vehicle treatment. Immunohistochemical analysis of ischemic-reperfused myocardial tissue demonstrated activation of classical complement pathway by deposition of C1q on cardiac myocytes and cardiac vessels. In addition, expression of the endothelial adhesion molecules P-selectin and intercellular adhesion molecule 1 (ICAM-1) was observed after reperfusion of the ischemic myocardium. In this regard, C1 INH administration abolished expression of P-selectin and ICAM-1 on the cardiac vasculature after myocardial ischemia and reperfusion. Blocking the classical complement pathway by exogenous C1 INH appears to be an effective means to preserve ischemic myocardium from injury after 24 and 48 hr of reperfusion. The mechanisms of this cardioprotective effect appears to be due to blocking of complement activation and reduced endothelial adhesion molecule expression with subsequent reduced PMN-endothelium interaction, resulting in diminished cardiac necrosis.
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PMID:Blocking of classical complement pathway inhibits endothelial adhesion molecule expression and preserves ischemic myocardium from reperfusion injury. 965 88

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

Platelet fibrinogen receptor (GPIIb/IIIa) antagonists clinically improve the effectiveness of thrombolysis or PTCA in treatment of acute myocardial infarction. 7E3Fab, the chimeric Fab fragment of a monoclonal GPIIb/IIIa antibody, reduces the incidence of death, reinfarction or restenosis in patients and may improve blood flow and regional wall motion in reperfused myocardium. Besides inhibition of platelet aggregation, 7E3Fab may block fibrinogen bridging between the polymorphonuclear neutrophil (PMN) adhesion molecule MAC-1 and platelet GP IIb/IIIa, thus attenuating interaction of platelets with PMN. Experimentally, the interaction of platelets with PMN exacerbated postischemic myocardial stunning. In our own studies in isolated guinea pig hearts, human PMN, platelets and fibrinogen where simultaneously infused during the initial reperfusion period after 15 min of global ischemia. FACS analysis of cells in the coronary effluant revealed that 7E3Fab reduced platelet GP IIb/IIIa expression to 10% of baseline. PMN-platelet aggregate formation in the coronary effluate was markedly reduced by 7E3Fab, parallel to a decrease of PMN-platelet aggregates found by in situ double fluorescence microscopy in the postischemic coronary vasculature. The inhibition of PMN-platelet aggregate formation by 7E3Fab treatment coincided with a significant improvement of external heart work, which suffered a 50% reduction after ischemia, reperfusion, and exposure to PMN, platelets and fibrinogen. Obviously, application of 7E3Fab inhibits formation and coronary retention of PMN-platelet aggregates in the postischemic, reperfused myocardium. This effect may contribute to the clinically observed beneficial effects of this adjuvant treatment after myocardial ischemia.
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PMID:Effects of endothelium/leukocytes/platelet interaction on myocardial ischemia--reperfusion injury. 1115 4


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