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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review discusses the role of three mediators synthesized by the vascular endothelium, which are involved in maintaining the surface of the endothelial cells in a non-thrombogenic state. Prostacyclin, discovered in 1976, is a product of arachidonic acid metabolism. This labile prostanoid, with a chemical half life of approximately three minutes, relaxes vascular smooth muscle and inhibits the aggregation of blood platelets. Endothelium-derived relaxing factor (EDRF), discovered in 1980, is even more labile than prostacyclin with a half life counted in seconds. It also relaxes smooth muscle and inhibits the aggregation and adhesion of platelets. Recently, it has been identified as nitric oxide. Prostacyclin and EDRF are released together following stimulation of receptors on endothelial cells and cooperate to inhibit platelet aggregation and adhesion. 13-HODE, acts from inside the cell to make the endothelial surface less adhesive and is not released. These mediators act together to form the endothelial defence mechanism against adhering blood cells. Underproduction can lead to diseases such as hypertension or atherosclerosis. A mainly fish diet, rich in eicosapentaenoic acid alters the prostacyclin/thromboxane balance in favour of prostacyclin-like activity. This type of diet may provide protection against atherosclerosis and myocardial infarction.
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PMID:Mediators and the anti-thrombotic properties of the vascular endothelium. 264 8

Altered arterial wall shear stress may adversely affect vascular endothelium and contribute to atherogenesis. This study examined the hypothesis that, in humans, dilation of normal coronary arteries with increased flow limits increases in shear stress and that loss of flow-mediated dilation in atherosclerosis results in failure to control shear stress. Coronary blood flow was increased by infusing adenosine (0.022 to 2.2 mg/min) through a 2.5F Doppler flow catheter positioned in the middle segment of the left anterior descending coronary artery in 8 patients with mild atherosclerosis but no flow-limiting stenosis and in 10 patients with entirely smooth coronary arteries. Quantitative angiography and coronary flow velocity were used to estimate shear stress in a proximal segment of the left anterior descending artery exposed to increased flow, but not to adenosine. The peak increase in blood flow was the same in smooth (371 +/- 65%) and irregular (377 +/- 50%) arteries. However, at peak flow, dilation was greater in smooth segments (16.3 +/- 2.7%) than in irregular segments (2.0 +/- 1.5%) (p less than 0.001). In each patient, smooth segments dilated with increasing shear stress (slope 7.4 +/- 0.9%), whereas irregular segments dilated less (slope 0.9 +/- 0.6%) and showed greater increases in shear stress (p less than 0.01). The peak increase in shear stress was less in smooth (189 +/- 23%) than in irregular (365 +/- 52%) segments (p less than 0.01). These results suggest a control mechanism in normal coronary arteries whereby increases in shear stress stimulate vasodilation and thus limit further increases in this force at the endothelial surface.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Control of shear stress in the epicardial coronary arteries of humans: impairment by atherosclerosis. 280 73

These recommendations for secondary prevention of clinical coronary cardiopathy are the result of a symposium attended by 46 experts belonging to the councils on arteriosclerosis, clinical cardiology, epidemiology, and prevention and rehabilitation of the International Society and Federation of Cardiology. Secondary prevention of coronary cardiopathy refers to measures designed to prevent deterioration or death in patients with clinical manifestations of coronary cardiopathy. Such measures in addition to drugs include health actions that may improve the status of various coronary risk factors: the patient's life style should stress maintenance of proper weight, regular physical exercise, reduction of saturated fats and cholesterol in the diet, and elimination of smoking and excessive alcohol consumption. It is considered reasonable to control hypertension through the most innocuous means possible, but findings of the few existing controlled studies of effects of treatment of hypertension in coronary cardiopathy are complex. Drug treatment may be necessary for most patients, but nondrug measures should be added when possible. Various proofs including results of some controlled studies justify the recommendations for reducing elevated levels of serum cholesterol and low density lipoprotein cholesterol through dietary measures. Optimum plasma cholesterol levels are 5.2 mmol/1 or less, and the upper limit is 5.7 mmol/1. The rules for secondary prevention are the same for diabetics as for nondiabetics, but some special precautions are necessary in diabetics. Habitual and vigorous physical activity has been associated with a decline in the incidence of coronary cardiopathy in different population studies, although there has been no demonstration that exercise can alter the progression of atherosclerosis or improve collateral circulation. Stress should be recognized as a risk factor and included in secondary prevention, but the concept that stress is the key risk factor in coronary events is in conflict with a large body of scientific evidence. Oral contraceptives (OCs) tend to increase boood pressure and weight as well as serum triglyceride levels, and to reduce glucose tolerance and high density lipoprotein cholesterol in some formulations. OCs also affect the integrity of the vascular endothelium and alter blood coagulation, fibrinolysis, and platelet function. These thrombogenic changes are intensified with age, especially after 35, and with smoking. OCs are innocuous in women under 35 with no history of venous or arterial disease or pulmonary embolism and who have normal blood pressure and serum cholesterol levels. Patients using OCs should control their blood pressure and weight and be alert to any symptoms of thrombotic episodes. The risk/benefit ratio of longterm estrogen treatment in meno- and postmenopausal women with coronary cardiopathy has not yet been established. Apart from 1 study in primates, there is no evidence that vasectomy should be considered either indicated or contraindicated for coronary patients. Beta blockers, platelet function inhibitors, anticoagulants, and other drugs are under active study for secondary prevention of coronary cardiopathy.
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PMID:[Recommendations for secondary prevention of the clinical coronary cardiopathy]. 285 11

The interaction of blood platelets with collagen is generally considered to be of primary importance in the arrest of bleeding and to have a role in the pathogenesis of thrombosis and atherosclerosis. Following damage to the vascular endothelium, circulating platelets come into contact with exposed collagen fibrils in the subendothelium and spread along it; this is followed by the secretion of several biologically active substances and by aggregation of platelets. The glycoproteins of the platelet plasma membrane have an important role in the mechanisms underlying these processes. So far, two specific defects of platelet function in patients with a bleeding disorder are known to be associated with a glycoprotein defect and the study of these patients has contributed significantly to present concepts of platelet function. The glycoprotein (GP) IIB-III complex, absent or deleted in the aggregation-defective Glanzmann's thrombasthenia, has been identified as the platelet fibrinogen receptor. GPIb, which is absent in the adhesion-defective Bernard-Soulier syndrome, has been identified as the von Willebrand factor receptor on platelets. We now report a defect of the platelet plasma membrane glycoprotein composition in a patient whose platelets are totally unresponsive to collagen.
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PMID:Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. 293 89

Endothelial cells form the intimal lining of the entire vascular system. The vascular endothelium is continuously and directly bathed by components of the bloodstream and represents the initial fixed anatomical surface with which these components come in contact. In the past decade, the methodologies for studying endothelial cell functions have markedly advanced, enabling direct and detailed study of the vascular endothelium. From such studies, it is now apparent that the vascular endothelium represents an extraordinarily complex network of cells demonstrating a multitude of distinct anatomic, metabolic, and immunologic properties critical to such processes as angiogenesis, atherosclerosis, thrombosis, neoplasia, and a variety of metabolic disorders including homocystinuria and diabetes mellitus. This report will focus on the interactions of insulin and the insulin-like growth factors (IGFs) with vascular endothelium, based on studies with cultured endothelial cells, isolated microvessels, and perfused organ systems. Data will be presented relevant to the following concepts: (1) endothelial cells, in culture and in vivo, have specific receptors for insulin, IGF-I, and IGF-II; (2) insulin, IGF-I, and IGF-II have both distinct and overlapping functions in cultured endothelial cells; (3) cultured endothelial cells process receptor-bound insulin, IGF-I, and IGF-II, by distinct processes; (4) in vivo, capillary endothelial receptors are integrally involved in the transport of intact insulin to subendothelial sites of insulin action; and (5) vascular endothelium has specialized cellular features that are likely to contribute to the unique interactions of endothelial cells with insulin and the IGFs.
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PMID:Insulin, insulin-like growth factors, and vascular endothelium. 297 48

Oxidative damage to the vascular endothelium may play an important role in the pathogenesis of atherosclerosis and aging, and may account in part for reduced vascular prostacyclin (PGI2) synthesis associated with both conditions. Using H2O2 to induce injury, we investigated the effects of oxidative damage on PGI2 synthesis in cultured endothelial cells (EC). Preincubation of EC with H2O2 produced a dose-dependent inhibition (inhibitory concentration [IC50] = 35 microM) of PGI2 formation from arachidonate. The maximum dose-related effect occurred within 1 min after exposure although appreciable H2O2 remained after 30 min (30% of original). In addition, H2O2 produced both a time- and dose-dependent injury leading to cell disruption, lactate dehydrogenase release, and 51Cr release from prelabeled cells. However, in dramatic contrast to H2O2 effects on PGI2 synthesis, loss of cellular integrity required doses in excess of 0.5 mM and incubation times in excess of 1 h. The superoxide-generating system, xanthine plus xanthine oxidase, produced a similar inhibition of PGI2 formation. Such inhibition was dependent on the generation of H2O2 but not superoxide in that catalase was completely protective whereas superoxide dismutase was not. H2O2 (50 microM) also effectively inhibited basal and ionophore A23187 (0.5 microM)-stimulated PGI2 formation. However, H2O2 had no effect on phospholipase A2 activity, because ionophore A23187-induced arachidonate release was unimpaired. To determine the effects on cyclooxygenase and PGI2 synthase, prostaglandin products from cells prelabeled with [3H]arachidonate and stimulated with ionophore A23187, or products formed from exogenous arachidonate were examined. Inhibition of cyclooxygenase but not PGI2 synthase was observed. Incubation of H2O2-treated cells with prostaglandin cyclic endoperoxide indicated no inhibition of PGI2 synthase. Thus, in EC low doses of H2O2 potently inhibit cyclooxygenase after brief exposure whereas larger doses and prolonged exposure are required for classical cytolytic effects. Surprisingly, PGI2 synthase, which is known to be extremely sensitive to a variety of lipid peroxides, is not inhibited by H2O2. Lipid solubility, enzyme location within the EC membrane, or the local availability of reducing factors may explain these results, and may be important determinants of the response of EC to oxidative stress.
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PMID:Effect of hydrogen peroxide on prostaglandin production and cellular integrity in cultured porcine aortic endothelial cells. 299 39

Arachidonic acid (AA) is metabolized by the cyclo-oxygenase and the lipoxygenase pathways to give a number of products, some of which have potent and sometimes opposing biological activities. Different cell types produce different metabolites, so that the chief AA metabolite produced by the platelet is the pro-aggregatory thromboxane A2 (TXA2), whereas that produced by the vascular endothelium is the anti-aggregatory prostacyclin. White blood cells, on the other hand, are the chief source of the leukotrienes, which are implicated in the inflammatory process. Generation of these products may be modified in certain pathological conditions, such as atherosclerosis and diabetes, where prostacyclin synthesis is reduced and TXA2 synthesis increased, resulting in a pro-thrombotic state. Synthesis of AA metabolites may be inhibited, either totally or selectively, using drugs which inhibit different enzymes in the metabolic pathway. These drugs may be beneficial in the treatment of thrombotic disorders and inflammation. AA metabolism may also be modified by dietary substitution with eicosapentaenoic acid, a fatty acid present in fish oils.
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PMID:Arachidonate metabolism in blood cells and the vessel wall. 301 65

Although a superficial similarity exists between the musculoskeletal disorders associated with natural aging and those of progeria, an in-depth analysis reveals profound differences in the pathophysiology between the two processes. The protean manifestations of progeria can best be explained on the basis of the vascular changes found at autopsy. A disorder of the vascular endothelium may predispose progeric vessels to atherosclerotic changes. The unique musculoskeletal manifestations of progeria arise from the effects of premature atherosclerosis on the vascularized connective tissues.
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PMID:The musculoskeletal manifestations of progeria. A literature review. 304 91

"Primary" cilia were present in the endothelial cells of human aortic fatty dots and streaks but not in those of normal intima. They had the features of cilia of the "9 + 0" axonemal configuration observed in many other cells. A lateral foot process and transitional fibers "anchored" the ciliary basal body in the cytoplasm, but rootlets were not identified in material examine. Ladder-like configurations interconnected the two centrioles (= diplosome) of control endothelium. The "primary" cilia of endothelium differed from those of the rudimentary type observed in smooth muscle cells in similar lesions of man, but shared many features with cilia of those present in experimental atherosclerosis in rabbit. Cilia were rarely described in vascular endothelium. It is believed that, to date, they were not reported to occur in normal or pathological arteries in man. It is being stressed that whereas the significance of these unusual organelles remains uncertain, their widespread occurrence may indicate that their role is more important than was believed previously, and they should cease being a curiosity only.
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PMID:Endothelial cilia in human aortic atherosclerotic lesions. 310 Dec 81

The vascular endothelium, in response to pulsatile flow and vasoactive agents including acetylcholine, secretes the endothelium-derived relaxing factor (EDRF), a substance which regulates vascular tone. Recent interest in EDRF has focused on its possible dysfunction in atherosclerosis. In animal models of the disease, endothelium-dependent relaxation is markedly reduced. The continuous exposure of the endothelium in hyperlipidaemia to high concentrations of low-density lipoprotein (LDL), a known atherogenic risk factor, may explain this dysfunction. Here, we demonstrate that pathophysiological concentrations of LDL directly inhibit endothelium-dependent relaxation. Chemically modified LDL, in contrast, is inactive, implying that the inhibition is through a receptor-dependent mechanism.
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PMID:Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta. 310 33


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