Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several pieces of evidence suggest that vascular endothelium may be a site of latent herpetic viral infection, and that activation of such infection might cause or aggravate atherosclerosis. The present studies which utilized HSV-1 infection of cultured endothelial monolayers, provide insights into two phenomena seemingly relevant in considerations of atherosclerosis. Thus, mechanisms are reported by which infected endothelium may be damaged by marginated inflammatory cells, and be transformed from an anticoagulant to a procoagulant tissue. First, granulocytes are attracted to, and avidly bind, endothelium infected for very brief periods. This interaction is associated with denudation of intact cells as well as actual cytolysis through release of PMN proteases and toxic oxygen species. Second, several potentially additive abnormalities of HSV-infected endothelium would seem to foster coagulation. These include: a) its loss of surface heparans and thrombomodulin; b) its inability to synthesize prostacyclin with associated incapacity to deter platelet adhesion; c) its disordered membrane lipid conformation which is likely associated with excessive surface thrombin generation; and d) its unique ability to generate and release tissue factor. We speculate that mechanical abrasion may reactivate latent herpes (HSV or CMV) infection in endothelial cells particularly those exposed to high shear forces--for instance, at vessel bifurcations. This may underlie the endothelial damage, clotting and atheroma formation commonly found at these sites.
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PMID:Herpes virus infection of endothelium: new insights into atherosclerosis. 132 3

Endothelial cells produce the 21-amino acid peptide endothelin, which is formed from its precursor, big endothelin, via the activity of converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1, and hypoxia. In vascular smooth muscle, endothelin binds to a specific receptor (ETA-subtype), which activates phospholipase C, leads to the formation of inositol trisphosphate, diacylglycerol (which activates protein kinase C), and increased intracellular Ca2+. In certain blood vessels, the endothelin receptor on vascular smooth muscle is linked to a voltage-operated Ca2+ channel via a G-protein. This explains why Ca2+ antagonists inhibit endothelin-induced contractions in certain, but not all, blood vessels. In the human forearm circulation, Ca2+ antagonists do prevent endothelin-induced contractions and unmask endothelin-induced vasodilation mediated by endothelial prostacyclin production (via the ETB-receptor). The pulmonary circulation plays an important role in the metabolism of endothelin, as the lungs take up large quantities of the peptide during passage. Endothelin has profound vasoconstrictor effects in the pulmonary circulation (and also in bronchial tissue), and its production is augmented in pulmonary hypertension. In systemic hypertension, the circulating endothelin levels appear to be normal. In atherosclerosis and other forms of vascular disease, circulating endothelin levels are increased. Thus, endothelin is a potent mediator in the systemic and pulmonary circulation and, in particular, in diseases of the vasculature.
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PMID:Endothelin: systemic arterial and pulmonary effects of a new peptide with potent biologic properties. 133 60

Old concepts of an "inert" vascular endothelium have been entirely discredited. It is now known that the vascular endothelium and media form a "functional unit", communicating via both electric and humoral signals. Normal endothelium maintains vascular dilation through release of various dilatory substances, the main one being endothelial relaxing factor (EDRF), which is nitric oxide (NO). EDRF is, for example, released in response to increased shear stress that accompanies high flow rates, and acts by engaging the cyclic GMP system of smooth muscle cells. Even potential vasoconstrictors such as vasopressin, catecholamines and serotonin release EDRF. Endothelial release of prostacyclin supplements the EDRF action. EDRF (and prostacyclin) also inhibit platelet aggregation. In the presence of hypertension and/or atherosclerosis, endothelial function is often impaired and pressor/thrombogenic factors such as endothelin, thromboxane, vasopressin, catecholamines, and serotonin become more dominant. Antihypertensive therapy should, ideally, seek to restore endothelial function to normal.
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PMID:Hypertension and endothelial function--aspects of atheroma protection. 134 64

Results of animal studies suggest that calcium antagonists can inhibit the development of experimentally induced atherosclerosis. Although the biological process underlying this phenomenon has not been fully elucidated, several mechanisms have been proposed. Notably, calcium antagonists may suppress free radical-induced damage of the vascular endothelial cells with the consequent transport of low-density lipoproteins across the vascular endothelium and the accumulation of the lipids in the intima. Studies have shown that calcium antagonists can inhibit the stimulatory effects of epidermal growth factor on intracellular calcium concentrations and DNA synthesis in cultured rat aortic smooth muscle cells, but not those of platelet-derived growth factor or somatomedin C. Further experimental studies have demonstrated that calcium antagonists stimulate prostacyclin production and inhibit 12-hydroxyeicosatetraenoic acid-induced vascular smooth muscle cell migration, therefore preventing platelet aggregation and intimal thickening, respectively. Despite the encouraging results in animals, comparatively few clinical studies have been undertaken to establish the efficacy of calcium antagonists in the prevention of cardiovascular disease in hypertensive patients. This, in part, is due to the technical difficulties associated with measuring coronary artery stenosis, but the recent development of a technique for the video-densitometric analysis of coronary angiograms has enabled stenotic regions to be quantified. Using this approach, a retrospective study has been undertaken of the efficacy of long-term treatment with a calcium antagonist on the progression of coronary atherosclerosis. Results are encouraging and a prospective long-term, multicenter trial is proposed.
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PMID:The role of calcium antagonists in the treatment of atherosclerosis and hypertension. 136 1

Isradipine, a calcium antagonist of the dihydropyridine type, shows antiatherosclerotic actions that interfere with all three main mechanisms of atherosclerosis. These actions are mediated by the release of prostaglandin I2 and endothelium-derived relaxing factor, and the subsequent elevation of intracellular adenosine-3',5'-cyclic phosphate and 3',5'-guanosine monophosphate, respectively. These mechanisms have been proven in vitro and in animal models. Preliminary data in humans suggest that these mechanisms have clinical relevance in the long-term treatment of patients as well.
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PMID:Antiatherosclerotic actions of isradipine. 137 31

The familial correlations of prostacyclin and thromboxane levels were examined in 90 children and adolescents from 70 families with hereditary coronary heart disease and in 56 of the same age from 38 families without hereditary atherosclerosis and their parents. The genetic factors were demonstrated to make a significant contribution to the phenotypic dispersion of prostanoids. The familial predisposition to the disease was ascertained to modify the pattern of familial correlations of prostacyclin and thromboxane levels as compared with no predisposition. The influence of familial and environmental factors was found to be more pronounced in the families of patients with coronary heart disease, and one of the important sequelae is thromboxane hyperproduction in the patients' wives.
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PMID:[Phenotypic familial correlations of prostacyclin and thromboxane A2 levels in children and adolescents with or without hereditary predisposition to ischemic heart disease]. 140 59

Several epidemiological studies have shown decreased cardiovascular mortality and a lower incidence of coronary artery disease in subjects with high dietary intakes of Omega-3 polyunsaturated fatty acids. It has since been shown that Omega-3 fatty acids have a number of beneficial effects in the prevention of atherosclerosis in man: reduction of blood pressure, modifications of lipoprotein metabolism, modifications of haemostasis (increased bleeding time and reduced platelet aggregation), decreased plasma fibrinogen, modifications of the metabolism of arachidonic acid and its derivatives (decreased thromboxane and leukotriene synthesis, increased prostacyclin synthesis). Therefore, Omega-3 polyunsaturated fatty acids have several beneficial effects on the presumed mechanisms of atherogenesis and/or its complications: they could represent an original and seductive solution to the problem of prevention of cardiovascular disease.
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PMID:[Potential value of omega-3 polyunsaturated fatty acids in the prevention of atherosclerosis and cardiovascular diseases]. 141 9

Spontaneous acute occlusion of the coronary artery produces regional myocardial ischemia and infarction. This coronary occlusion could be due to rapid progression of atherosclerosis or vasospasm. The factors that can precipitate an acute attack of myocardial infarction or coronary spasm are not known. It is proposed that a stress-induced rise of unesterified arachidonic acid could trigger a leukocyte respiratory burst with the release of free radicals such as superoxide anion (O2-), hydrogen peroxide, hydroxyl radical, and singlet oxygen. These free radicals have the ability to inhibit prostacyclin (PGI2) formation and enhance the breakdown of endothelium-derived vascular relaxing factor (EDRF) which are potent vasodilators and platelet anti-aggregators. This may lead to rapid progression of atherosclerosis or coronary vasospasm leading to acute myocardial infarction. If this is true, free radical quenchers and inhibitors of leukocyte oxidative burst may be useful in the prevention of progression of atherosclerosis and coronary vasospasm.
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PMID:Can free radicals induce coronary vasospasm and acute myocardial infarction? 143

Ten patients have been studied for lipidic behaviour during hemodialysis using as anticoagulant heparin and prostacyclin. Hearing has been administered at infusion rate of 2000 U/h and prostacyclin in 5 ng/kg/min. Lipidic behaviour (before and after hemodialysis) has been studied for apolipoproteins A and B, total serum cholesterol and serum triglycerides, HDL-cholesterol, lipoprotein. Total serum cholesterol/HDL-cholesterol, apolipoproteins A/apolipoproteins B, apolipoproteins A/HDL-cholesterol ratios have been also studied. Our findings show that heparin produces acute changes in lipidic behaviour after hemodialysis and suggest that administrations may contribute to lipidic derangement of uremic dialytic patient while heparin free dialysis (prostacyclin infusion) doesn't show lipidic derangement after dialytic treatment. Prostacyclin infusion suggests that may be a useful anticoagulant and therapeutic drug especially in uremic dialytic subject with high atherosclerosis involvement, dyslipidemia and arterial hypertension.
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PMID:[Lipid behavior during hemodialysis using heparin and prostacyclin]. 149 59

We investigated the effect of 22-oxa-1,25-dihydroxyvitamin D3, a synthetic analogue of vitamin D3, on the production of prostacyclin by vascular tissues using rat aortic rings and A7r5 cells derived from fetal rat aortic smooth muscle. Prostacyclin synthesis by aortic rings of rats treated with 22-oxa-1,25-dihydroxyvitamin D3 was much higher than that of non-treated controls, but did not cause any significant hypercalcemia. Treatment with 22-oxa-1,25-dihydroxyvitamin D3 significantly increased the production of prostacyclin by A7r5 cells for 48 hours in a dose-dependent manner. In time-course studies, cells incubated with 22-oxa-1,25-dihydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 produced prostacyclin progressively over a period of 48 hours. The shortest period of incubation that produced a significant amount of prostacyclin compared with control cultures was 24 hours. We observed that treatment with 22-oxa-1,25-dihydroxyvitamin D3 induced cyclooxygenase mRNA in A7r5 cells. Our data suggest that 22-oxa-1,25-dihydroxyvitamin D3 may possibly be a protective substance against the development of atherosclerosis by modulating prostaglandin metabolism.
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PMID:A synthetic analogue of vitamin D3, 22-oxa-1,25-dihydroxy-vitamin D3, stimulates the production of prostacyclin by vascular tissues. 151 73


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