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

Interactions between vascular endothelium and low density lipoprotein (LDL) have been implicated in the development of atherosclerosis. The effect of normal and oxidized LDL (Ox-LDL) on prostaglandin release by cultured adult human saphenous vein endothelial cells was investigated. Ox-LDL induced a rapid release of prostacyclin (PGI2) to levels which were several-fold higher than those observed with control LDL. PGI2 release was concentration-dependent and was biphasic, with a first peak occurring within 30 minutes (followed by a decrease), and a second peak occurring after several hours of incubation. PGI2 production was inhibited by lipoprotein-depleted serum and by indomethacin, an antagonist of cyclooxygenase activity. These cells produced mainly PGF2 alpha, with some PGE2 and PGI2 when stimulated by the ionophore A23187 at confluency. However, among these prostanoids, mainly PGI2 was produced in response to Ox-LDL. The data indicate that Ox-LDL induces the production of PGI2 by human vascular endothelial cells. Since Ox-LDL is cytotoxic, this phenomenon may be a manifestation of an early response to injury.
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PMID:Oxidized low density lipoprotein stimulates prostacyclin production by adult human vascular endothelial cells. 314 46

Vascular cell procoagulant activity may be important in the pathogenesis of atherosclerosis. In previous studies, we described the ability of the atherogenic metabolite homocysteine to activate endothelial cell Factor V, a key coagulation cofactor for thrombin generation. The present study was designed to investigate Factor V activity and Factor Xa-catalyzed prothrombin activation by control and atherosclerotic aorta from normal and hypercholesterolemic rabbits. Factor Xa generated ninefold more thrombin on atherosclerotic aortic segments than on control segments. Atherosclerotic segments activated 125I-prothrombin with Factor Xa in the presence of the thrombin inhibitor dansyl arginine-4-ethylpiperidine amide and cleaved 125I-Factor V. This suggests that increases in vessel-wall Factor V activity and Factor Xa-catalyzed prothrombin activation result from activation of vessel-wall Factor V. 125I-Factor Va peptides generated by atherosclerotic aorta were very similar in molecular weight to those generated by homocysteine-treated cells. When vascular endothelium was mechanically removed by brushing, atherosclerotic vessels still generated four- to fivefold more thrombin than control vessels. These data and results from immunocytochemical studies suggest that Factor V in atherosclerotic vessels is associated with both endothelium and other cells of the lesion. In contrast, Factor V in control vessels is associated primarily with endothelium. The increases in Factor V activity and thrombin formation in the blood vessel wall of hypercholesterolemic rabbits may contribute to the development of atherosclerosis and its complications.
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PMID:Formation of factor Va by atherosclerotic rabbit aorta mediates factor Xa-catalyzed prothrombin activation. 316 15

Different patho-anatomical and functional factors are considered to be involved in patients with unstable angina pectoris. Among these are a pre-existing plaque based on coronary atherosclerosis, the development of fissures or dissections of the plaque (often combined with thrombus formation at the site of the plaque) coronary vascular tone, and theoretically primary aggregation of platelets at a site of apparently normal vascular endothelium. Several comprehensive studies on patients who died from acute myocardial infarction or unstable angina, have convincingly shown that complications of an atherosclerotic plaque like fissures, dissections and thrombus formation may be present in 60 to 90% of cases. In addition, two groups of investigators, who have applied coronary angioscopy for direct visualization of offending coronary arteries, have confirmed these results, since in about 60-80% of patients with unstable angina complicated atheromata, i.e. rupture, ulceration, thrombus formation, could be documented, whereas in all patients with stable angina an uncomplicated atheroma was seen angioscopically. On the basis of these results a hypothetical sequence of events in patients with stable angina, unstable angina and acute myocardial infarction has been proposed. Stable angina pectoris may be seen in patients with uncomplicated atheroma in one of the major coronary artery branches. When dissections, ulcerations and thrombus formation occur as a complication of a formerly smooth plaque, patients show the clinical syndrome of unstable angina. If an occlusive thrombus develops, the patient will run into a fresh myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathophysiology of unstable angina pectoris--correlations with coronary angioscopic imaging. 324 55

Cholesterol oxidation products (oxysterols) found in foods may be atherogenic, possibly by altering the barrier function of the vascular endothelium. To investigate this hypothesis, endothelial cells were cultured on micropore filters and the effect of cholesterol and the oxysterol cholestan-3 beta,5 alpha,6 beta-triol (Triol) on albumin transfer across cultured vascular endothelial monolayers (ECM) was studied. Exposure to Triol significantly increased albumin transfer across ECM. The effect of Triol on endothelial cell barrier function was time and concentration dependent, with maximum albumin transfer being reached at 20 microM Triol and after a 24-h exposure. Pure cholesterol, on the other hand, did not affect albumin transfer at concentrations as high as 130 microM. Although an increase in albumin transfer across ECM was observed after a 2-h incubation with Triol-enriched media, a 24-h incubation period was necessary to cause a significant release of cellular lactate dehydrogenase (LDH) into the culture media. Morphological perturbations of the cell monolayers were observed at approx. 14-18 h after cell exposure to Triol-enriched media. Enrichment with cholesterol or vitamin E did not prevent the Triol-induced increase in albumin transfer across ECM. These results suggest that exposure to oxidized cholesterol, but not cholesterol, itself, reduces the ability of the endothelium to act as a selectively permeable barrier to plasma components, and that these events may not be prevented by cholesterol or vitamin E.
Atherosclerosis 1987 Dec
PMID:Cholestan-3 beta,5 alpha,6 beta-triol decreases barrier function of cultured endothelial cell monolayers. 342 58

Physical activity plays an important role in the prevention of ischaemic heart disease. However, data on the mediating mechanisms are only partly established, and concentrated mainly on plasma lipoproteins. Prostanoids, especially prostacyclin and thromboxane, through their effects on vascular endothelium, platelet function, and interaction with lipoproteins, are postulated to be centrally involved in the pathogenesis of atherosclerosis. The reported acute effects of physical activity on prostanoids and platelet function are contradictory and may be considered both beneficial and unfavourable. On the other hand, although even less is reported on the response to regular exercise, data appear more favourable in relation to atherosclerosis. Currently, data on physical activity and prostanoids, including both acute and chronic effects, are limited and necessitate additional, systematic studies on dose-response relationships.
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PMID:Physical activity and prostanoids. 353 5

Low fluid dynamic shear acting on the vascular endothelium has been suggested as a factor in atherogenesis. This study describes qualitatively differences of wall shear rate in the left anterior descending coronary artery (LAD) of man and relates the distribution of wall shear to that of atheromatous plaques. Selective coronary arteriograms of 21 patients without obstructive LAD diseases were reviewed. Blood velocity, and therefore wall shear in the LAD, was assessed qualitatively based upon the rate of clearance of contrast material. There was a rapid clearing of contrast material along the outer wall of the LAD as it curved around the border of the heart. A much slower clearing occurred along the inner wall, bordering the myocardium, which persisted two to six cardiac cycles after the outer wall had cleared. This suggests that velocity, and therefore shear rate, is lower along the inner wall of the LAD than along the outer wall. In 27 patients who died of noncardiac disease, an uneven distribution of atheromatous plaques in the LAD was observed histologically, with greater involvement of the inner wall. These observations demonstrate an association between the lower shear rate along the inner wall of the LAD and the site of higher concentration of atherosclerosis.
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PMID:Relation of atherosclerosis to arterial wall shear in the left anterior descending coronary artery of man. 375 57

Arteriosclerotic lesions have been produced in monkeys (Macaca nemestrina) by selective removal of the vascular endothelium with an intra-arterial balloon catheter. Immediately after de-endothelialization a platelet layer covers the denuded area. This thrombus is gradually removed and by 7 days the vessel appears to be largely reendothelialized. Beginning at day 4, smooth muscle cells undergo modification and migrate through fenestrae in the internal elastic lamina into the intima where they proliferate. By 28 days, the intimal lesion consists of multiple layers of smooth muscle cells surrounded by collagen and elastic fibers and basement-like material. After 3 months the lesions are markedly hyperplastic and contain new extracellular connective tissue elements. In contrast, with no further injury after 6 months the lesion has decreased markedly in size suggesting that it may be reversible in the absence of continued endothelial injury. The importance of endothelial "injury" exposing medial smooth muscle to plasma constituents may be the principal factors associated with the migration and proliferation of the smooth muscle cells into the intima resulting in the lesion. The smooth muscle cells do not contain lipid. The similarities of this lesion to the fibromusculo-elastic lesion or preatherosclerotic intimal hyperplasia in man makes it a useful model for the further study of atherosclerosis.
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PMID:Experimental arteriosclerosis. I. Fibrous plaque formation in primates, an electron microscope study. 462 50

Prostacyclin is a potent vasodilator and platelet inhibitor produced by vascular endothelium. Endogenous production of prostacyclin under physiologic conditions is extremely low, far below the capacity of vascular tissue to generate this substance in response to stimulation in vitro. This may reflect a low frequency or intensity of stimulation of prostacyclin production. We postulated that if prostacyclin does act as an endogenous platelet-inhibitory agent, it should be produced in greater amounts in a clinical setting in which platelet-vascular interactions are likely to be increased. To test this hypothesis, we examined prostacyclin biosynthesis in patients with severe atherosclerosis and evidence of platelet activation in vivo. Excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha, a major urinary prostacyclin metabolite, was significantly higher in 9 patients with severe atherosclerosis and evidence of platelet activation (251 to 1859 pg per milligram of creatinine) than in 54 healthy volunteers (45 to 219 pg per milligram of creatinine; P less than 0.001). This difference represented an alteration in biosynthesis rather than in metabolism, since the fractional conversion of infused prostacyclin to the dinor metabolite was identical in both groups. Prostacyclin production may be low in healthy persons because there is almost no stimulus for its production but enhanced in patients with severe atherosclerosis as a consequence of platelet interactions with endothelium or other vascular insults. These observations are compatible with a role for prostacyclin as a local regulator of platelet-vascular interactions.
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PMID:Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. 623 83

The mechanism of glucose entry into human vascular endothelial cells was studied in monolayer cultures of normal (primary) and virally (SV40) transformed umbilical vein endothelium. Radioisotopic uptake studies with the glucose analogues 2-deoxy-D-glucose, and 3-O-methyl-D-glucose, and the nonmetabolizable stereoisomer L-glucose, indicated the presence of a saturable, stereospecific hexose carrier mechanism in both cell types. In other experiments with D-glucose and 3-O-methyl-D-glucose, the phenomenon of countertransport was demonstrable. Hexose transport was not affected by KCN, dinitrophenol, or ouabain, but was inhibited by phloretin and phlorizin in a pattern consistent with facilitated diffusion. Kinetic constants were obtained for both 2-deoxy-D-glucose and 3-O-methyl-D-glucose uptake. Similar Km values (range, 3.3-4.7 mM) were noted with normal and transformed cells, whereas the apparent Vmax was 0.56 nmol/microliter cytosol/minute for primary cells and 1.7-2.5 nmol/mu cytosol/minute for transformed cells. Under standard culture conditions, as well as following 18 hours of serum deprivation, insulin at concentrations up to 10(-5) M did not appear to influence hexose uptake in either cell type. Metabolism of 14C(U)-D-glucose to 14CO2 also was not stimulated by insulin. The presence of an insulin-insensitive, facilitated transport system for glucose in vascular endothelium has relevance for glucose metabolism in this tissue, and potentially for the association of certain vascular diseases (e.g., diabetic microangiopathy, atherosclerosis) with altered glucose homeostasis.
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PMID:Hexose transport in normal and SV40-transformed human endothelial cells in culture. 626 Aug 23

Glucose in concentrations of 20 mg% (or greater) significantly inhibited 14C-labelled ascorbic acid (1.25 mg%) uptake in endothelial cells in the presence of insulin (1600 microU/ml). The absence of insulin also significantly reduced ascorbic acid uptake. Furthermore, this reduction could be exacerbated by glucose (40, 160 mg%) but not equimolar concentrations of fructose. Increased ascorbic acid concentrations (two-fold) in the absence of insulin (1) significantly enhanced uptake, and (2) reversed the inhibition of glucose. These findings support earlier reports that ascorbic acid uptake into the cell may be compromised by decreased insulin and/or increased extracellular glucose levels. Since previous animal studies have correlated experimental ascorbic acid deficiencies with atherogenic processes (presumably by altering glycosaminoglycan metabolism), the postulation that the "diabetic condition" (low insulin, hyperglycemia) accelerates the cellular changes leading to atherosclerosis by impairing ascorbic acid uptake into the vascular endothelium, may now be supported.
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PMID:The effects of glucose on ascorbic acid uptake in heart endothelial cells: possible pathogenesis of diabetic angiopathies. 636 63


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