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)

Recent investigations have suggested that the vascular endothelium is an active participant in the regulation of arterial tone and blood flow. In a state of health, the endothelium contributes to hemodynamic equilibrium; however, it rapidly becomes dysfunctional in hypercholesterolemia and diabetes mellitus or with exposure to the stress of hypertension or long-term smoking. Among the deficits observed during endothelial dysfunction is a reduction in the synthesis and release or an excessive degradation of EDRF. This potent vasorelaxant is derived from the amino acid L-arginine and has been characterized as NO or a closely related substance. EDRF relaxes vascular smooth muscle by activating guanylate cyclase. A deficiency in the activity of EDRF may be the mechanism of diminished coronary vasodilation in patients with ischemic heart disease. Organic nitrates, which are metabolized to NO or S-nitrosothiol at the cellular level, are often used in the management of myocardial ischemia; they also induce vasodilation by activating guanylate cyclase. The similarities between organic nitrates and endogenous EDRF and their interactions are discussed in this review.
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PMID:Endothelium, coronary vasodilation, and organic nitrates. 783 12

Atherosclerosis is characterized by hypertrophy of the vascular media, intimal thickening and lipid-containing plaques. Atherosclerosis is a progressive systemic vascular disease which leads to impaired tissue perfusion due to vascular obstruction. In advanced stages it is often complicated by thrombosis. Recent research demonstrates that atherosclerosis is also a functional disease. In atherosclerosis and hypercholesterolemia, normal vasodilatation is impaired due to endothelial dysfunction. In addition, the ability of the vessel wall to reject adhering and aggregating platelets is deteriorated. Endothelial dysfunction in atherosclerosis is characterized by impaired formation of nitric oxide (NO), formerly known as endothelium-derived relaxing factor (EDRF). NO is continuously formed in the vascular endothelium and promotes tissue perfusion by relaxation of vascular smooth muscle. Endogenously formed NO may also protect against foam cell formation and media hypertrophy, i.e. against the structural component of atherosclerosis. In patients with ischaemic heart disease, the endothelial dysfunction leads to decreased ability to dilate the coronary vessels in response to several forms of physiological stimuli. Endothelial dysfunction in atherosclerosis is reversed by lipid-lowering therapeutic interventions.
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PMID:Nitric oxide (NO) in the cardiovascular system: role in atherosclerosis and hypercholesterolemia. 786 90

Neutrophil (PMN) adhesion to the vascular endothelium is an important mechanism of myocardial reperfusion injury. The adhesion process is initially mediated by selectins (e.g., P- and L-selectin), and monoclonal antibodies directed against these adhesion molecules exert cardioprotective activity in ischemia/reperfusion models. The counterreceptors for these selectins are thought to be carbohydrate-containing moieties. In this connection, we studied the effect of a soluble sialyl Lewisx-containing oligosaccharide (SLex-OS) on PMN-endothelial interactions in a feline model of myocardial ischemia/reperfusion (MI/R). SLex-OS (10 mg/kg), administered 10 min before R, significantly reduced myocardial necrosis compared with its vehicle 270 min after reperfusion (6 +/- 1% vs. 35 +/- 4% of area at risk, P < 0.01). The cardioprotection was confirmed by significantly lower plasma creatine kinase activities in SLex-OS vs. vehicle-treated cats (P < 0.01). Cardiac contractility (dP/dt max) of cats receiving SLex-OS was significantly preserved after 270 min of R (97 +/- 2% vs. 78 +/- 5% of initial, P < 0.01). Furthermore, endothelium-dependent relaxation to acetylcholine in coronary artery rings isolated from MI/R cats treated with SLex-OS was significantly preserved (73 +/- 7% vs. 22 +/- 6% vasorelaxation, P < 0.01). In vitro PMN adherence to coronary vascular endothelium after 270 min of R was significantly attenuated in the SLex-OS-treated group compared with the vehicle group (14 +/- 5 vs. 91 +/- 12 PMN/mm2, P < 0.01). Our results indicate that a SLex-OS is cardioprotective and preserves coronary endothelial function after MI/R, indicating an important role of sialyl Lewisx in PMN accumulation, endothelial dysfunction, and myocardial injury in myocardial ischemia/reperfusion.
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PMID:Sialyl Lewisx-containing oligosaccharide attenuates myocardial reperfusion injury in cats. 790 2

Myocardial ischaemia may occur during spasm or thrombosis of the coronary arteries. The vascular endothelium plays an essential role in the lesions observed during ischaemia and myocardial reperfusion by the intermediary of the numerous endothelium-derived vasoactive factors. These include the "endothelium-derived relaxing factors" (EDRFs) nitrous oxide, prostacyclin, which are vasodilators and platelet antiaggregants ant the "endothelium-derived contracting factors" (EDCFs), endothelin, PGH2, oxygen-free radicals which are vasoconstrictive. The endothelial cells also produce the platelet activating factor and factors essential for coagulation. The metabolism and biological properties of these different mediators are reviewed. During the phenomena of myocardial ischemia-reperfusion, endothelial regulation is activated by tissue hypoxia and reduction of coronary flow and perfusion pressure. This regulation also depends on the functional state of the arteries (macroscopically normal or pathological). These vasomotor phenomena are associated with the effects of platelet aggregation and myocardial accumulation of neutrophil polynuclear blood cells. During the second phase of reperfusion cellular lesions are produced by the generation of cytotoxic oxygen-free radicals. Assays of mediators present a clinical interest when the modalities of sampling have been fixed (systemic blood samples or during cardiac catheterisation, sites of sampling, choice of timing of sampling with respect to the biological half lives of the mediators). Determining a correlation between the in vitro biological effects on those in isolated organs and clinical data has become possible with the improvement in techniques of sampling and the increasing collaboration between biologists and clinicians.
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PMID:[Mediators of the vascular endothelium as markers of myocardial ischemia and reperfusion]. 830 14

The recent discovery that the endothelium synthesizes several powerful vasodilators, including prostacyclin and endothelium-derived relaxing factor, has substantially changed our view of the importance of the vascular endothelium and the perspective from which we consider the mechanisms of vascular control. It is now known that the vascular endothelium plays a key role in circulatory homeostasis through its ability to sense the local vascular milieu and respond to it by the synthesis and release of a variety of biologically active substances. The endothelium influences not only vascular tone, but also vascular remodeling via the production of growth-promoting and growth-inhibiting substances; hemostasis and thrombosis through antiplatelet, anticoagulant, and fibrinolytic effects; and inflammation through the expression of chemotactic and adhesion molecules on the cell membrane. In diseases such as atherosclerosis, however, these functions of the endothelium are impaired and may even become counterproductive and disease-promoting. The "activated" or injured endothelial cells paradoxically become prothrombotic, growth-promoting, and leukocyte-adhesive. The endothelium also loses its vasodilating ability, rendering the underlying vascular smooth muscle susceptible to a preponderance of vasoconstrictive forces. It is now recognized that these disturbances in endothelial function are principal players in the ischemic manifestations of coronary artery disease. Endeavors to modify or reverse endothelial dysfunction may therefore be of significant therapeutic benefit in the treatment of myocardial ischemia. This review outlines several important insights into the biology of the arterial wall that are currently being applied to the study of coronary artery disease in humans.
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PMID:Role of endothelium in ischemic coronary syndromes. 837 98

In the past decade the importance of the vascular endothelium in cardiovascular pathophysiology has become more apparent. One substance that is synthesised by and stored in endothelial cells is von Willebrand factor (vWF). When released, vWF seems to mediate platelet aggregation and adhesion to the vascular endothelium. Because the release of vWF is increased when endothelial cells are damaged, vWF has been proposed as an indicator of endothelial disturbance or dysfunction. The availability of such an index of endothelial dysfunction may have clinical value, because measurement of such a marker can be a non-invasive way of assisting in diagnosis or as an indicator of disease progression. The known association between vWF, thrombogenesis, and atherosclerotic vascular disease also suggests that high concentrations of vWF may be an indirect indicator of atherosclerosis and/or thrombosis. In addition, high vWF concentrations have prognostic implications in patients with ischaemic heart disease and peripheral vascular disease.
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PMID:von Willebrand factor and its relevance to cardiovascular disorders. 854 Nov 59

Hyperlipidemia following successful renal transplantation is a frequent and persistent disorder, and lipid abnormalities are associated with ischemic heart disease. Correlates have been found to cyclosporine and steroids as the major causes of lipid disorders. Cardiovascular disease is currently the major cause of death among renal graft recipients in the long run. Therefore, lipid lowering therapy appears to be useful in those patients without cardiovascular disease (primary prevention) and is mandatory in those with established coronary artery disease (secondary prevention). Because of the multiplicity of other cardiovascular risk factors, hyperlipidemia might only be of minor importance. On the other hand, lipids may even accelerate the development of arteriosclerosis in a preinjured vascular endothelium. Dietary modification or reduction of dietary fat is considered to be the first line of antilipemic therapy. Unfortunately, hyperlipidemia appears not to be responsive to modification of dietary fat without weight reduction. In general, patients taking immunosuppressive drugs after organ transplantation are grouped under high risk population when pharmacological intervention is selected, since only some lipid lowering drugs are safe and efficacious in short-term studies and when used with precaution. Low-dose HMG-CoA reductase inhibitor is the drug of choice for lowering LDL cholesterol. Immunosuppression withdrawal protocols have successfully been used to control massive hyperlipidemia in immunologically stable patients in the long term. Although evidence from prospective controlled intervention studies is lacking, it is reasonable to adopt the principle of a broad-based approach aimed at reducing LDL cholesterol as well as other major risk factors for cardiovascular disease in this patient population. The likelihood is that effective control of serum lipids and lipoproteins may achieve a similar beneficial reduction in absolute mortality in renal transplant recipients as already demonstrated in individuals without kidney disease but with cardiovascular damage.
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PMID:Clinical utility of antilipidemic therapies in chronic renal allograft failure. 858 86

Hyperhomocyst(e)mia (Hcy) negatively influences vascular endothelium and coagulation factors. Association of Hcy with premature arteriosclerosis (rather than atherosclerosis), stroke, myocardial infarction and peripheral arterial and venous disease was proved in clinical and epidemiological studies, even as the association with conventional risk factors like age, male sex, smoking, hypertension and hypercholesterolemia. Vitamin substitution of folates, vitamin B6 and B12 decreases Hcy blood levels, however definite evidence is still lacking, whether it results in lower incidence and mortality from cardiovascular diseases. Therefore clinical and epidemiological studies are necessary. Before the grant-application we proved in a pilot study significantly higher Hcy levels in 97 patients with manifest ischaemic heart disease than in 37 controls.
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PMID:[Homocysteine, a less well-known risk factor in cardiac and vascular diseases]. 870 81

Although several studies have demonstrated that chronic exposure to estrogen appears to be cardioprotective, acute circulatory effects of estrogen are largely unknown. Therefore, we studied the effects of acute administration of 17 beta-estradiol in myocardial ischemia/reperfusion. Cats were subjected to 90 min of left anterior descending coronary artery (LAD) occlusion and 270 min of reperfusion (MI/R). Either the estrogenic steroid, 17 beta-estradiol or its non-estrogenic isomer, 17 alpha-estradiol was administered (i.v.) 30 min prior to reperfusion at 1 microgram/kg bolus followed by a constant infusion lasting the remaining duration of the protocol at 1 microgram/kg/h. Control cats were subjected to sham MI/R. Cats treated with 17 beta-estradiol demonstrated a marked reduction in cardiac necrosis following MI/R compared to cats receiving 17 alpha-estradiol or phosphate buffered saline (17 +/- 2% v 33 +/- 1% or 34 +/- 4% area of necrosis indexed to the area-at-risk, P < 0.01). In addition, cats receiving 17 beta-estradiol exhibited reduced myocardial PMN infiltration in necrotic tissue as compared to 17 alpha-estradiol treated cats. Moreover, 17 beta-estradiol administration attenuated neutrophil adherence to ex vivo coronary vascular endothelium compared to the two controls (44 +/- 8 PMNs/mm2 v 79 +/- 7 PMNs/mm2 or 86 +/- 7 PMNs/mm2 P < 0.01). These data indicate that 17 beta-estradiol protects against myocardial ischemia/reperfusion, in part, by attenuating PMN infiltration and subsequent injury due to PMN mediator release.
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PMID:Protection from myocardial reperfusion injury by acute administration of 17 beta-estradiol. 876 38

Nitric oxide (NO), derived from the vascular endothelium or other cells of the cardiovascular system, has an important role in physiological regulation of blood flow and has pathophysiological functions in cardiovascular disease. The mechanisms and enzymes involved in the biosynthesis of NO and biological actions of NO, including vasodilatation, cytotoxicity and inflammation, are briefly reviewed. These reactions involving NO cause pathological disturbances of arterial function, coronary blood flow regulation, and may contribute to cardiac myocyte dysfunction. NO and prostacyclin (PGI2), which is also released from the endothelium, act synergistically to inhibit platelet aggregation and adhesion, and in some arteries these mediators also synergise in terms of vasodilatation. In addition, NO is capable of hyperpolarizing vascular smooth muscle, but activation of the endothelium may cause hyperpolarization and may thus promote vasodilatation by an additional mechanism. After myocardial ischemia and reperfusion, production of NO and superoxide radicals represent important mechanisms of cytotoxicity, causing injury to the coronary endothelium and myocytes and compromising ventricular contractile function. Moreover, upon reperfusion endothelium-dependent vasodilatation is impaired and the coronary arteries constrict, leading to irregular myocardial perfusion. This is a consequence of the accumulation of activated leucocytes that we found to generate endogenous inhibitors of NO. These factors have yet to be fully characterised, but clearly they may have a role in irregularities of myocardial reperfusion and cellular injury. Chronic heart failure is associated both with impairment of endothelium-dependent vasodilatation and with excess production of NO via the inducible NO synthase (iNOS), although it is unclear whether the latter assists or compromises ventricular contractile performance under these conditions. Disturbances in the activity of isoforms of NO synthase in the artery wall also accompany the development of atherosclerosis, providing conditions propitious for vasospasm and thrombosis, and perhaps contributing to cell proliferation. Reversing these NO defects with therapeutic agents including angiotensin converting enzyme (ACE) inhibitors offers promise in protecting against some manifestations of vascular disease.
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PMID:Nitric oxide in coronary artery disease: roles in atherosclerosis, myocardial reperfusion and heart failure. 880 87


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