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)

Endothelial dysfunction is a key event in cardiovascular disease. Measurement of endothelial dysfunction in vivo presents a major challenge, but has important implications since it may identify the clinical need for therapeutic intervention, specifically in primary prevention. Several biological markers have been used as indicators of endothelial dysfunction. The soluble adhesion molecules sICAM-1 and sVCAM-1 lack specificity and are increased in inflammatory processes. Both markers are increased in coronary artery disease. sICAM-1 level predicts the risk for cardiovascular disease or diabetes mellitus in healthy individuals. sE-selectin is specific for the endothelium and is increased in coronary artery disease and diabetes mellitus. sE-selectin is also associated with diabetic risk. The endothelium-specific marker, soluble thrombomodulin, is associated with severity of coronary artery disease, stroke or peripheral occlusive arterial disease and is not increased in healthy or asymptomatic subjects. Interestingly, thrombomodulin decreases during treatment of hypercholesterolemia or hyperhomocysteinemia. In contrast, von Willebrand factor is the best endothelial biomarker and predicts risk for ischemic heart disease or stroke.
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PMID:Circulating markers of endothelial function in cardiovascular disease. 1653 Jan 77

This study assesses the relation between qualitative and quantitative findings of myocytes and interstitial connective tissue in the ischemic heart disease. Qualitative and quantitative changes of myocytes and interstitial connective tissue were studied on the serial cross myocardial sections from 20 autopsied hearts with ischemic lesions, stained by immunohistochemistry using a monoclonal antibody (von Willebrand factor) and with hematoxylin-eosin method. Myocardial sections included proximal and distal part of occlusion and area of occlusion of coronary vessels. The volume densities (V V) of the cardiac myocytes and interstitial fibrosis in the group with coronary occlusion were examined stereologically and compared with control group. The findings showed a significant reduction in the volume density of myocytes and an increase in the volume density of interstitial fibrosis in patients with coronary occlusion compared with control group. Significant reduction in the volume density of myocytes and an increase in volume density of interstitial fibrosis were greater in the distal part of occlusion and area of occlusion, than in the proximal part of the occlusion. Our stereological results give useful quantitative information's of changes in myocardium parts during coronary occlusion as well as in normal conditions, and represent objective proof of significant changes in ischemic myocardium described by qualitative analyses.
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PMID:Morphologic findings of the ischemic myocardium. 1653 87

Beraprost sodium, an orally active prostacyclin analogue, has vasoprotective effects such as vasodilation and antiplatelet activities. We investigated the therapeutic potential of beraprost for myocardial ischemia. Immediately after coronary ligation of Sprague-Dawley rats, beraprost (200 microg/kg/day) or saline was subcutaneously administered for 28 days. Four weeks after coronary ligation, administration of beraprost increased capillary density in ischemic myocardium, decreased infarct size, and improved cardiac function in rats with myocardial infarction. Beraprost markedly increased the number of CD34-positive cells and c-kit-positive cells in plasma. Also, four weeks after coronary ligation of chimeric rats with GFP-expressing bone marrow, bone marrow-derived cells were incorporated into the infarcted region and its border zone. Treatment with beraprost increased the number of GFP/von Willebrand factor-double-positive cells in the ischemic myocardium. These results suggest that beraprost has beneficial effects on ischemic myocardium partly by its ability to enhance neovascularization in ischemic myocardium by mobilizing bone marrow cells.
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PMID:Beraprost sodium enhances neovascularization in ischemic myocardium by mobilizing bone marrow cells in rats. 1697 84

To understand the heterogeneity of platelets, we investigated the correlation between hemostatic factors and the platelet index [platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR) and platelet distribution width (PDW)] in patients with ischemic heart disease (IHD). Ninety-seven patients with IHD and 120 aged controls (AC) were enrolled in the study. D-dimer, thrombin-antithrombin III complex (TAT), von Willebrand factor antigen (VWF:Ag) and platelet indexes were measured in the peripheral venous blood. The D-dimer and TAT levels in the patients were significantly elevated compared to the AC. VWF:Ag was also elevated, but not significantly so. However, no differences were observed in the platelet index between the patients and the AC. In the patients, the level of VWF:Ag was significantly inversely correlated with the platelet count, but such correlations were not observed in the D-dimer and TAT. TAT was significantly positively correlated with MPV, P-LCR and PDW. VWF:Ag was also correlated, though not significantly, with MPV, P-LCR and PDW. The D-dimer was not correlated with the platelet index. In the AC, the platelet count was inversely correlated with VWF:Ag, but not significantly so. VWF:Ag showed significant positive correlations with MPV, P-LCR and PDW. However, the D-dimer and TAT were not correlated with the platelet index in AC. These findings suggest that VWF:Ag and TAT seem to be profoundly related to platelet volume.
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PMID:Relationship between hemostatic factors and the platelet index in patients with ischemic heart disease. 1723 41

Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immune-compromised mouse AMI model was studied. Enhanced green fluorescent protein-labeled hMSCs from IHD patients (hMSC group: 2 x 10(5) cells in 20 microl, n = 12) or vehicle only (medium group: n = 14) were injected into infarcted myocardium of NOD/scid mice. Sham-operated mice were used as the control (n = 10). Cardiac anatomy and function were serially assessed using 9.4-T magnetic resonance imaging (MRI); 2 wk after cell transplantation, immunohistological analysis was performed. At day 2, delayed-enhancement MRI showed no difference in myocardial infarction (MI) size between the hMSC and medium groups (33 +/- 2% vs. 36 +/- 2%; P = not significant). A comparable increase in left ventricular (LV) volume and decrease in ejection fraction (EF) was observed in both MI groups. However, at day 14, EF was higher in the hMSC than in the medium group (24 +/- 3% vs. 16 +/- 2%; P < 0.05). This was accompanied by increased vascularity and reduced thinning of the infarct scar. Engrafted hMSCs (4.1 +/- 0.3% of injected cells) expressed von Willebrand factor (16.9 +/- 2.7%) but no stringent cardiac or smooth muscle markers. hMSCs from patients with IHD engraft in infarcted mouse myocardium and preserve LV function 2 wk after AMI, potentially through an enhancement of scar vascularity and a reduction of wall thinning.
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PMID:Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction. 1764 73

Exocytosis of endothelial granules promotes thrombosis and inflammation and may contribute to the pathophysiology of early reperfusion injury following myocardial ischemia. TAT-NSF700 is a novel peptide that reduces endothelial exocytosis by inhibiting the ATPase activity and disassembly activity of N-ethylmaleimide-sensitive factor (NSF), a critical component of the exocytic machinery. We hypothesized that TAT-NSF700 would limit myocardial injury in an in vivo murine model of myocardial ischemia/reperfusion injury. Mice were subjected to 30 minutes of ischemia followed by 24 hours of reperfusion. TAT-NSF700 or the scrambled control peptide TAT-NSF700scr was administered intravenously 20 minutes before the onset of ischemia. Myocardial ischemia/reperfusion caused endothelial exocytosis, myocardial infarction, and left ventricular dysfunction. However, TAT-NSF700 decreased von Willebrand factor levels after myocardial ischemia/reperfusion, attenuated myocardial infarct size by 47%, and preserved left ventricular structure and function. These data suggest that drugs targeting endothelial exocytosis may be useful in the treatment of myocardial injury following ischemia/reperfusion.
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PMID:Inhibition of N-ethylmaleimide-sensitive factor protects against myocardial ischemia/reperfusion injury. 1793 25

Heterotopic cardiac xenotransplantation from alpha1,3-galactosyltransferase gene-knockout (GalT-KO) swine to baboons was performed to characterize immunological reaction to the xenograft in the absence of anti-Gal antibody-mediated rejection. Eight baboons received heterotopic cardiac xenografts from GalT-KO porcine donors. All baboons were treated with chronic immunosuppressive therapy. Both histological and immunohistochemical studies were performed on biopsy and graftectomy samples. No hyperacute rejection was observed. Three baboons were euthanized or died 16 to 56 days after transplantation. The other five grafts ceased beating between days 59 and 179 (median, 78 days). All failing grafts exhibited thrombotic microangiopathy (TM) with platelet-rich fibrin thrombi in the microvasculature, myocardial ischemia and necrosis, and focal interstitial hemorrhage. TM developed in parallel with increases in immunoglobulin (IgM and IgG) and complement (C3, C4d, and C5b-9) deposition, as well as with subsequent increases in both TUNEL(+) endothelial cell death and procoagulant activation (increased expression of both tissue factor and von Willebrand factor and decreased expression of CD39). CD3(+) T-cell infiltration occurred in all grafts and weakly correlated with the development of TM. In conclusion, although the use of GalT-KO swine donors prevented hyperacute rejection and prolonged graft survival, slowly progressive humoral rejection--probably associated with non-Gal antibodies to the xenograft--and disordered thromboregulation represent major immunological barriers to long-term xenograft survival.
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PMID:Thrombotic microangiopathy associated with humoral rejection of cardiac xenografts from alpha1,3-galactosyltransferase gene-knockout pigs in baboons. 1846 6

121 patients aged 35 to 85 years with ischemic heart disease (IHD) were observed. All the patients formed two age groups, mature and elderly. The 1st group consisted of women aged 35 to 55 years and men aged 35 to 60 years, the 2nd group of women aged 55+ years and men aged 60+ years. The group of control consisted of 47 patients aged 18 to 56 years without authentically verified IHD. 11 (9.1%) patients died of cardiovascular reasons within one year from the moment of hospitalisation. All of them (middle age 71.4 +/- 7.4 years) were the patients of elderly age grouP. The regression analysis showed that among various parameters (increase level of protein in urine, urea, creatinine, IL-6 and von Willebrand factor in blood, heart contraction rate), the growth of level of myeloperoxidase accompanied by activity reduction of glutathione reductase in neutrophils has also been connected with the increase of lethal outcome risk. Besides in elderly patients unlike patients of mature age in the beginning of hospitalisation a decrease in antioxidative protection activity (catalase) in neutrophils accompanied by an increase in IL-6 contents in blood not depended on presence diabetes mellitus type II and not connected with systolic dysfunction of heart left ventricle was found. It is possible to believe, that oppression antioxidative protection of neutrophils coming in process of ageing of an organism promotes in the conditions of stress uncontrollable manufacture reactive forms of oxygen damaging endothelium and breaking hemostasis, which results in death.
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PMID:[Age changes redox regulation metabolism and antioxidative protection of neutrophils in patients with ischemic heart disease]. 1943 75

Over the past fifteen years, numerous observations have linked Helicobacter pylori (H. pylori) infection to ischemic heart disease (IHD). Despite the controversial literature data, it has been postulated that if a role is plausible, it will be in the early events of the acute coronary syndrome. According to this model, we focused on the potential pathogenic mechanisms relating H. pylori to IHD like platelet aggregation and thrombosis. To identify all publications in this field, a MEDLINE search of studies published in English from 1965 to 2009 was conducted. Although very few investigations were found, these showed data of paramount importance. In particular, it has been demonstrated that some strains of H. pylori bind von Willebrand factor and interact with glycoprotein Ib to induce platelet aggregation in humans. In experiments from animal models, such infection promoted the formation of platelet aggregates by both a marked increase in the flux of rolling leukocytes and the appearance of platelet and leukocyte-platelet aggregates in gastric venules. This aggregate formation was abrogated by antibodies against specific adhesion molecules (L- and P-selectin). The future challenge is to gain more knowledge in this field and to translate these information into clinical practice.
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PMID:Potential link between Helicobacter pylori and ischemic heart disease: does the bacterium elicit thrombosis? 2046 11

Prostaglandin E2 (PGE2) has been reported to modulate angiogenesis, the process of new blood vessel formation, by promoting proliferation, migration and tube formation of endothelial cells. Endothelial progenitor cells are known as a subset of circulating bone marrow mononuclear cells that have the capacity to differentiate into endothelial cells. However, the mechanism underlying the stimulatory effects of PGE2 and its specific receptors on bone marrow-derived cells (BMCs) in angiogenesis has not been fully characterized. Treatment with PGE2 significantly increased the differentiation and migration of BMCs. Also, the markers of differentiation to endothelial cells, CD31 and von Willebrand factor, and the genes associated with migration, matrix metalloproteinases 2 and 9, were significantly upregulated. This upregulation was abolished by dominant-negative AMP-activated protein kinase (AMPK) and AMPK inhibitor but not protein kinase, a inhibitor. As a functional consequence of differentiation and migration, the tube formation of BMCs was reinforced. Along with altered BMCs functions, phosphorylation and activation of AMPK and endothelial nitric oxide synthase, the target of activated AMPK, were both increased which could be blocked by EP4 blocking peptide and simulated by the agonist of EP4 but not EP1, EP2 or EP3. The pro-angiogenic role of PGE2 could be repressed by EP4 blocking peptide and retarded in EP4(+/-) mice. Therefore, by promoting the differentiation and migration of BMCs, PGE2 reinforced their neovascularization by binding to the receptor of EP4 in an AMPK-dependent manner. PGE2 may have clinical value in ischemic heart disease.
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PMID:Prostaglandin E2 promotes endothelial differentiation from bone marrow-derived cells through AMPK activation. 2187 56


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