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

It has recently been found that endothelial cells exhibit an unusual change in cellular behavior in response to contact with fibrin. The possible implications of this finding with regard to the mechanism of atherogenesis are discussed. It is proposed that mural fibrin in vivo may produce a disorganized endothelium which can act as a nidus for further fibrin deposition and platelet aggregation. In the presence of inadequate fibrinolysis, a prolonged endothelial lesion could occur which may eventually result in atheromatous plaque formation. This view of atherogenesis requires reduced fibrinolytic activity as a prerequisite for plaque formation, a requirement which is in agreement with currently known data associating atherogenic risk factors with inhibited fibrinolysis.
Atherosclerosis 1979 Aug
PMID:Fibrin and atherogenesis--a hypothesis. 50 84

Some features of the aortic intima were examined with the scanning electron microscope (SEM) and found to contribute to the etiology of dissecting aneurysm. The endothelium over intimal plaques was not as pendulous as endothelium surrounding plaques. The pendulous appearance of aortic endothelial cells could be associated with the contractile nature of these cells. Some undescribable factor, which has been termed stress or atherosclerosis, seemed to reduce the contractile nature of endothelial cells on the plaque areas. Analyses with SEM revealed a probable cause of a dissecting aneurysm. The effect of pulsating blood pressure on an inelastic endothelium could create a separation between endothelial cells and the fluid pressure of blood could then separate the tissue until the vessel ruptured into the body cavity or back into the aorta. Because all abdominal aortic segments examined had atherosclerosis, it was not possible to show the amount of intimal alteration between normal and atherosclerotic aortas. Each blood pressure line showed a similar change which was 4.52 and 4.95% for the high and low blood pressure lines, respectively. There were no demonstrable correlations in this study between either high or low blood pressure lines of turkeys and atherosclerosis.
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PMID:A comparison between aortic lumen surfaces of hypertensive and hypotensive turkeys. 51 58

Uncomplicated human atherosclerotic plaques often contain large amounts of cholesterol esters and solid cholesterol monohydrate crystals. If such plaques are to regress the crystalline cholesterol would have to dissolve and be transported out of the arterial wall. Since cholesterol is quite insoluble in water, dissolution of plaque crystals might occur through lipids in the plaque, specifically, the cholesterol esters. As part of a study on feasibility of plaque reversal we have studied a specific step involving the dissolution of cholesterol monohydrate into cholesterol ester oil. With specific considerations of the composition and physical state of the cholesterol ester solvent, the size and form of cholesterol monohydrate crystals, the agitation rate, the temperature and the presence of water, we have found that cholesterol esters are an efficient solvent for cholesterol monohydrate crystals. The rate of dissolution was fast reaching 90% of saturation in 1 h. We conclude dissolution of cholesterol monohydrate into cholesterol ester oil is not a rate-limiting step in reversal of the atherosclerotic plaque. We suggest that transport of dissolved cholesterol from cholesterol ester oil may limit the removal. If transport of dissolved cholesterol could be enhanced, cholesterol monohydrate crystals could be rapidly dissolved and facilitate reversal of atherosclerotic lesions.
Atherosclerosis 1978 Jul
PMID:The dissolution of cholesterol monohydrate crystals in atherosclerotic plaque lipids. 67 18

The morphological examination of advanced atherosclerosis caused by atherogenic diet in the coronary arteries and in the aorta abdominalis (trifurcation) of pigs showed plaque hemorrhage and signs of vascularisation. In these areas phagocytosis of erythrocytes could be observed. The cells involved in the phagocytic process vary considerably in size and shape but show common features of arterial smooth muscle cells. The modulation of smooth muscle cells is evident and progresses as the process of phagocytosis progresses. In early stages of erythrocyte engulfment the morphological characteristics which identify these cells as of smooth muscle origin are parts of surrounding basement membrane, caveolae intracellulares and myofilaments. The authors suggest, that under certain conditions arterial smooth muscle cells participate in phagocytic processes in the injured vessel wall as potential macrophages with lysosomal enzyme adaptation. Changes in extracellular surroundings and the actual situation of the vessel wall condition seem to play an important role in the induction of phagocytosis. Relations to vascularisation processes of the arterial plaques are evident.
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PMID:Erythrocytophagocytosis by arterial smooth muscle cells in experimental atherosclerosis. 68 84

Rabbits were maintained for 12 weeks on either a control or hypercholesteremic dietary regime, or on comparable diets supplemented with pyridinolcarbamate (PDC) at a level of 30 mg/kg body weight/day. Blood was obtained from all rabbits prior to study and at two-week intervals for analysis of serum cholesterol, phospholipid phosphorus and triglycerides. Animals from each group were sacrificed at 4-week intervals for quantitative assessment of the degree of atherosclerotic involvement of the aorta. All animals in the four groups consumed their entire daily allowance (100 g) of their respective diets, and weight gains throughout the feeding period were comparable in the 4 groups. PDC given with the control chow diet had no effect on serum cholesterol levels but did result in persistent decrease in serum triglycerides and a variable decrease in serum phospholipids during the 12-week feeding period. None of the rabbits on the chow diet, with or without PDC, had any evidence of aortic lesions during the experimental period. Rabbits fed 1% cholesterol administered with chow exhibited markedly elevated levels of serum cholesterol and phospholipids, while serum triglycerides were not significantly different than in the control group. In these animals there was a rapid and progressive increase in aortic atherosclerosis throughout the study, and at 12 weeks plaque involvement was 74 +/- 8% of the aortic surface. Addition of PDC to the 1% cholesterol--chow diet resulted in significantly lowered levels of serum cholesterol and phospholipids, but these remained elevated compared to the control levels. There was also a dramatic reduction in the rate and extent of aortic plaque formation. Thus, after 12 weeks on diet, only 27 +/- 6% of the aortic surface showed evidence of atheroma. The data suggest that PDC significantly decreases the hypercholesteremia resulting from feeding 1% cholesterol to rabbits, and that this may be largely responsible for the antiatherogenic effect of this drug.
Atherosclerosis 1978 Oct
PMID:Pyridinolcarbamate and experimental atherosclerosis. Correlation of hypocholesterolemic and antiatherogenic effects. 72 38

A strain of genetically selected White Carneau pigeons (WC-2) with increased atherosclerosis at similar plasma cholesterol concentrations as randomly bred (RBWC) pigeons was studied to evaluate the commonly known risk factors for atherosclerosis. Indicators for the presence of hypertension, diabetes mellitus, "stress", hyperuricemia and hypothyroidism were determined. In pigeons fed the atherogenic diet, major differences in atherosclerosis were seen between WC-2 and RBWC. WC-2 pigeons had more aortic surface covered with plaque and greater concentrations of aortic nonesterified cholesterol, esterified cholesterol, uronic acid, and hydroxyproline, as well as a greater prevalence and severity of coronary artery atherosclerosis. For WC-2 and RBWC pigeons we found similar levels of hypercholesterolemia, mean blood pressure, plasma triglyceride and glucose concentrations. In addition, several other physiological variables such as plasma uric acid, calcium and phosphorus concentrations, adrenal and thyroid weights which have been implicated in the pathogenesis of atherosclerosis were similar. The findings indicate that the differences in extent and severity of atherosclerosis between WC-2 and RBWC cannot be explained by differences in the risk factors studied. Possible genetic regulation of atherosclerosis by mechanisms operable in the arterial wall of WC-2 pigeons is suggested.
Atherosclerosis 1978 Dec
PMID:Risk factors in pigeons genetically selected for increased atherosclerosis susceptibility. 72 42

The purpose of this study was to test the effectiveness of various doses of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) in an experimental rabbit model of athero-arteriosclerosis designed by Hass et al. (Amer. J. Pathol., 49 (1966) 739). This model, which involves the feeding of a hypercholesterolemic diet in conjunction with the administration of moderately high doses of vitamin D and nicotine, results in an extensive arterial disease with complicated lesions. EHDP was administered daily by subcutaneous injection at levels of 0.25, 1.0 and 2.5 mg/kg body weight beginning with the initiation of the atherogenic regimen. Results of chemical and histopathological analyses after 8 and 12 weeks of treatment indicate the following: (1) There was a dose-related inhibition of arterial calcification at 8 weeks. At 12 weeks, only the 2.5 mg/kg dose of EHDP resulted in reduced calcification. (2) EHDP administration appeared to influence arterial lipid-containing plaque formation in medium sized arteries at 12 weeks. There was no apparent effect of EHDP administration on serum cholesterol and triglyceride levels. (3) EHDP, at a dose of 2.5 mg/kg/day, inhibited the vitamin D induced hypercalcemia. (4) EHDP administration at 2.5 mg/kg/day almost totally inhibited the thromboarteritis accompanying this disease. (5) The data thus indicate that if arterial calcification is inhibited, the other morphological effects of this treatment regime are also inhibited. This effect occurred even though serum lipid levels were unaffected. The data therefore emphasize the role of calcification in the pathogenesis of this type of experimental atherosclerosis and perhaps in human disease as well.
Atherosclerosis
PMID:The effect of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on a rabbit model of athero-arteriosclerosis. 81 8

The interrelationships between hypertension and atherosclerosis were investigated in a subhuman primate model (cynomolgus monkey) with hypertension produced by surgically coarcting the miathoracic aorta. The hypertensive coarcted monkey fed a low cholesterol diet for 6 months did not develop complicating atherosclerosis but did develop focal intimal lesions as well as marked thickening of the musculoelastic media of both the large and small arteries. Fibrocellular thickening of the intima and media occurred in the vessels proximal to the coarctation but not distal to the coarctation suggesting that a high level of blood pressure with resulting increase in arterial wall tension is responsible for these changes. The hypertensive coarcted monkey fed a hypercholesterolemic diet (2% cholesterol and 10% butter) for 6 months developed severe coronary atherosclerotic disease with fibrous plaque formation. The disease produced over 65% luminal narrowing of the major coronary arteries and their extramural and intramural branches. In contrast the noncoarcted normotensive animal fed the same diet developed mild atherosclerosis of only the major coronary arteries which caused an average luminal narrowing of 12%. Aggravation of atherosclerosis by hypertension also appeared to occur in the other arteries above the coarctation particularly the cerebral arteries. When the hypertensive coarcted monkey with preestablished coronary atherosclerosis was treated with a low cholesterol diet and a combination of antihypertensive drugs (hydrochlorothiazide, hydralazine, and reserpine), the progression of the disease was arrested. There also was evidence that treatment caused some regression of the coronary lesions which appeared to "heal" by fibrosis. The treatment of both hyperlipidemia and hypertension appeared to be more effective than the treatment of hyperlipidemia, alone.
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PMID:Aggravation of atherosclerosis by hypertension in a subhuman primate model with coarctation of the aorta. 81 49

Food and Drug Administration policy being considered for new marketed hypolipidemic agents includes: long-term safety to be demonstrated in postmarketing studies; evidence of clinical effectiveness to be demonstrated within a specified time period. Effectiveness is to be judged by one or more of the following: reduction in xanthomata, reduction atherosclerotic plaque, reduction in morbidity of coronary artery disease or peripheral and cerebral atherosclerosis, and reduction in mortality. Randomized double blind trials are deemed necessary.
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PMID:FDA considerations regarding new hypolipidemic agents. 83 24

Hypertension is associated with an increased incidence of generalized vascular disease. Antihypertensive drug therapy, while decreasing overall mortality due to cerebral hemorrhage, myocardial hypertrophy or renal failure, paradoxically does not appear to reduce the incidence of coronary atherosclerosis. This study investigates whether the drugs, as a possible side effect, may have an adverse influence on the development of atherosclerotic plaques. Groups of rabbits were fed an atherogenic diet containing 1% cholesterol for 12 weeks. Two commonly used antihypertensive agents (methyldopa and chlorthalidone) were added to the diet of some groups at levels of 100 mg and 10 mg per day respectively. No significant increase in total atherosclerotic plaque area was produced by either of the drugs tested singly or in combination. Plasma renin levels were only mildly elevated and in this experimental system there was no correlation between renin activity and atherosclerotic plaque intensity. There is thus no evidence from this study that antihypertensive drugs have any adverse effects on atherosclerotic plaque formation. While the ineffectiveness of these drugs against coronary atherosclerosis may indicate that normalization of pressure cannot arrest changes already initiated, it also supports the possibility that association of atherosclerosis with hypertension may be symptomatic of a common underlying defect not correlated by normalizing blood pressure.
Atherosclerosis 1977 Jan
PMID:Anti-inflammatory agents in experimental atherosclerosis. Part 2. Failure of antihypertensive drugs to exacerbate atherosclerotic plaque formation. 83 50


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