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

It has been proposed that low density lipoprotein (LDL) must undergo oxidative modification before it can participate in atherosclerosis. The present paper studied the effect of cholesterol oxidation in LDL on cultured vascular smooth muscle cells. LDL was oxidized by cholesterol oxidase (3-beta-hydroxy-steroid oxidase) which catalyzes the oxidation of cholesterol to 4-cholesten-3 one and other oxidized cholesterol derivatives. Cholesterol oxidase treatment of LDL did not result in lipid peroxidation. Cultured rabbit aortic smooth muscle cells were morphologically changed following exposure to cholesterol oxidized LDL. Nile red, a hydrophobic probe which can selectively stain intracellular lipid droplets, was applied to detect the cellular lipid content after treatment with oxidized or non-oxidized LDL cholesterol. LDL which did not undergo oxidation of its cholesterol had no effect on the cells. However, cellular nile red fluorescence intensity was increased as the pre-incubation time of cholesterol oxidase with LDL increased. This was supported by HPLC analysis which revealed that the oxidized cholesterol content of treated cells increased. These findings suggest that cholesterol oxidation of LDL can alter lipid deposition in the cells and change cell morphology. The oxidation of cholesterol in vivo may play an important role in the modification of LDL which could contribute to the generation of the lipid-laden foam cells.
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PMID:Effects of oxidative modification of cholesterol in isolated low density lipoproteins on cultured smooth muscle cells. 177 Sep 45

High K diets prevent hypertensive endothelial injury and intimal thickening. Cholesterol esters often deposit during hypercholesterolemia. We investigated whether a high K diet would influence cholesterol ester deposits in stroke prone SHR rats. Stroke prone SHR rats were fed for 3 months a basic diet containing 4% cholesterol, 14% coconut oil and 7% NaCl. One group of 13 rats had normal (.5%) K in the diet. Another group of 10 rats ate high (2.1%) K. Mean intra-arterial BPs averaged 165 mmHg in the normal K group and 161 mmHg in the high K group (NS). The serum cholesterol averaged 229 mg/dl in the normal K group and 214 in the high K group (NS). Total aortic cholesterol esters per rat averaged 187 micrograms in normal K vs 68 micrograms in high K, measured by gas chromatography. Thus high K reduced cholesterol ester deposits by 64% (p less than .0003), even though BPs and cholesterol levels were quite similar in the two groups. Both high cholesterol and high BP injure endothelial cells and increase invasion of monocytes and vascular smooth muscle cells into the intima and increase endothelial permeability to proteins. With high plasma cholesterol, these processes lead to atherosclerosis with cholesterol ester deposition. The high K diet, by protecting endothelial cells, can greatly decrease this cholesterol ester deposition. This effect could possibly be useful for preventing heart attacks in human hypertension.
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PMID:Cholesterol ester deposition is reduced in rats with hypercholesterolemia and hypertension. 177 92

To determine the relationship between plasma and arterial wall oxysterols, plasma and aortic tissue from 7 New Zealand White rabbits fed a high cholesterol (1%) diet for 6 weeks was compared to plasma and aortic tissue from 7 normocholesterolemic rabbits fed standard rabbit chow. Cholesterol and cholesterol oxide fractions were isolated and analyzed by gas chromatography. Normocholesterolemic plasma and aortic tissue contained low levels of cholest-5-ene-3 beta, 7 alpha-diol, cholesta-3,5-dien-7-one, 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol, cholest-5-ene-3 beta, 7 beta-diol, and 5 alpha-cholestane-3 beta, 5,6 beta-triol while hypercholesterolemic plasma and atherosclerotic aorta contained significantly higher levels (P less than 0.05) of these products. Furthermore, 5,6 beta-epoxy-5 alpha-cholestan-3 beta-ol not found in normocholesterolemic plasma or aortic tissue was present in substantial amounts in both hypercholesterolemic plasma and atherosclerotic aortic tissue. Cholest-5-ene-3 beta,25-diol and 3 beta-hydroxycholest-5-ene-7- one not present in normocholesterolemic aorta were present in the atherosclerotic aorta. The oxysterol chromatographic patterns of normocholesterolemic plasma and normocholesterolemic aortic tissue were similar to each other as were the oxysterol chromatographic patterns of hypercholesterolemic plasma and atherosclerotic aortic tissue. The chromatographic patterns between the normocholesterolemic and hypercholesterolemic samples differed however. Possible absorption of the low levels of cholesterol oxides present in the cholesterol feed could account for the elevation of only some of the oxysterols. We conclude that cholesterol oxides exist at some basal level in normocholesterolemia and that these levels are increased by cholesterol-feeding which results in hypercholesterolemia. Our findings demonstrate that there is a strong relationship between plasma and aortic arterial wall levels of cholesterol oxides and suggest that in addition to exogenous sources, formation of cholesterol oxides proceeds via free radical oxidation acting upon elevated cholesterol levels resulting in the accumulation of these potentially cytotoxic and atherogenic products.
Atherosclerosis 1991 Aug
PMID:Cholesterol feeding increases plasma and aortic tissue cholesterol oxide levels in parallel: further evidence for the role of cholesterol oxidation in atherosclerosis. 179 39

Serum and aortic tissue cholesterol levels in parallel with aortic relaxation to endothelium-dependent and independent drugs were determined in Watanabe heritable hyperlipidemic (WHHL) rabbits in comparison with New Zealand (N.Z.) normocholesterolemic rabbits, aged 4-14 months. Serum cholesterol was elevated (626 +/- 99 mg/100 ml) in 4-6-month-old WHHL rabbits and significantly lower in 12-14-month-old animals (344 +/- 51 mg/100 ml). Cholesterol infiltration in thoracic aorta was high in young WHHL compared with N.Z. rabbits (0.88 +/- 0.3 mg/100 mg fresh tissue vs. 0.08 +/- 0.003 mg/100 mg, respectively) and it did not vary with age. In N.Z. rabbits, serum and aortic cholesterol levels were low from 4 to 14 months of age. The aortic relaxation to acetylcholine (0.03-3 microM) on EC50 noradrenaline precontracted rings was similar in 4-6-month-old WHHL and N.Z. rabbits of the same age. In WHHL rabbits, the relaxation to acetylcholine was significantly reduced in 7-11- (-35% at maximum) and in 12-14-month-old rabbits (-40% at maximum). In N.Z. rabbits the response to acetylcholine was not modified in the 3 age groups. The relaxation to ATP (30 microM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits, but in 12-14-month-old WHHL rabbits the maximal relaxing response was significantly more elevated than in age-matched N.Z. rabbits (50.1 +/- 2.5% vs. 35.1 +/- 3.2%, respectively). The aortic relaxation to NaNO2 (10 microM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1991 Aug
PMID:Aortic response to relaxing agents in Watanabe heritable hyperlipidemic (WHHL) rabbits of different age. 179 50

A new text of the Dutch Cholesterol Consensus has been prepared by an expert committee, including general practitioners. Population screening is not advocated since the general cholesterol level in the Netherlands is higher than desired with regard to the atherosclerosis risk. Case-finding is advised in view of mutual enhancement of risk factor effects. Women and the elderly are not excluded from this strategy. Cholesterol levels should be measured repeatedly and if elevated, triglycerides and HDL-cholesterol levels should be measured also. If the cholesterol level is strongly elevated cholesterol synthesis inhibitors are medication of first choice.
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PMID:[Revision of consensus cholesterol]. 180 92

During the past decade, large, placebo-controlled, randomized trials have demonstrated that the incidence of coronary events can be reduced by treating hyperlipidemia. In studies with angiographic end points, marked lowering of total and low-density-lipoprotein cholesterol with comparable increases in high-density-lipoprotein cholesterol retards the progression of coronary atherosclerosis and favors regression. In the Cholesterol-Lowering Atherosclerosis Study (CLAS), such therapy also prevented the appearance and worsening of atherosclerotic lesions in coronary bypass grafts. In the recently reported Familial Atherosclerosis Treatment Study (FATS), in which coronary lesions were measured quantitatively, treatment induced clear regression of coronary atherosclerosis and also markedly decreased coronary events. The beneficial effect on coronary lesions in these studies appears to be proportional to the degree of lipid lowering. In addition, new evidence suggests that aspirin and calcium antagonists might prevent the development of early coronary lesions. The identification and aggressive treatment of patients with high serum cholesterol levels can have a major impact on the development and evolution of coronary atherosclerosis.
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PMID:Regression of coronary atherosclerosis: an achievable goal? Review of results from recent clinical trials. 186 31

Based on substantial evidence, the 1984 NIH Consensus Development Conference concluded that the treatment of total and low-density lipoprotein (LDL) cholesterol elevations with diet and, when necessary, with drugs, can reduce the risk of coronary artery disease (CAD). Accordingly, in 1988 the National Cholesterol Education Program (NCEP) published guidelines for defining moderate-, borderline-high-, and high-risk categories for CAD. Many clinical trials have supported the benefits of antihyperlipidemic therapy. Evidence from the Coronary Primary Prevention Trial gave rise to the "2:1 ratio," i.e., that a 1% reduction in total cholesterol level is associated with a 2% decrease in CAD events. The Helsinki Heart Study results indicated that additional benefit may be obtained by raising high-density lipoprotein (HDL)-cholesterol levels. Dramatic reductions in LDL and total cholesterol were achieved by the Program on the Surgical Control of the Hyperlipidemias, which also achieved a 35% reduction in CAD events and a two-thirds reduction in both coronary bypass operations and angioplasties. Long-term benefits of cholesterol lowering in terms of cardiovascular and all-cause mortality have been shown in the Coronary Drug Project and the Multiple Risk Factor Intervention Trial. Two major studies that have documented angiographic changes as a result of cholesterol lowering are the Cholesterol-Lowering Atherosclerosis Study (CLAS) and the Familial Atherosclerosis Treatment Study (FATS). In both CLAS and FATS, there was a decrease in the development of new lesions and a lowering of the rate of progression of existing lesions. In FATS, there was also evidence that aggressive antihyperlipidemic therapy will decrease existing lesions in some CAD patients.
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PMID:Rationale for treatment. 186 34

The effect of serum cholesterol on aortic, cerebral, coronary and femoral atherosclerosis as well as on the incidence of cerebral and myocardial infarctions were analyzed in 3,236 consecutive autopsies in the elderly. Serum cholesterol levels declined over the age of 80 in both genders. The cholesterol levels of females were significantly higher than that of males in each age group from the sixties through the nineties. The increase in serum cholesterol was correlated with the progression of coronary atherosclerosis in both genders, but not with cerebral or femoral atherosclerosis. Slight progression of aortic atherosclerosis was observed when serum cholesterol was over 160 mg/dl. Cholesterol induced progression of coronary atherosclerosis was found in cases with hypertension, but not in the normotensive group. In accordance with the progression of coronary atherosclerosis, the incidence of myocardial infarction increased with an elevation of serum cholesterol levels, and this relationship between myocardial infarction and cholesterol levels was found only in patients with hypertension. No correlation was found between the incidence of cerebral infarction and serum cholesterol levels. It was concluded that hypercholesterolemia in the elderly is a risk factor of myocardial infarction in cases with hypertension, but is not a risk factor of cerebral infarction.
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PMID:[Cholesterol, atherosclerosis and cerebro-cardiovascular complications in 3,236 elderly autopsy cases]. 187 Feb 84

Cultured aortic smooth muscle cells from rabbit, in synthetic and contractile state, are considered good models for studying pathological and normal cells, respectively, during the atherosclerotic process. Cholesterogenic activity was compared in cells which were obtained in both states of the same subculture and incubated with labeled sodium acetate. This activity (expressed as the percentage of total cell radioactivity uptake transformed into cholesterol) was very high in synthetic cells and comparable to that of cancer cells. Cholesterol synthesis was lower in contractile cells and similar to that observed in a nonpathological cultured cell. During the cell life-span (studied in two cultures) cholesterogenic activity initially increased and then slowly decreased, in the two phenotypic states. Near the end of the culture life, cholesterol production drastically decreased, but this was due to a blocking of the last steps, lanosterol demethylation and C27 sterol transformation into cholesterol, rather than to a sharp decrease in the first steps of the cholesterogenic process. Cells in the synthetic and contractile states released newly synthesized lipids which were essentially late precursors of cholesterol, but accumulation of oxy-sterols was not observed. The excretion of metabolites increased with culture aging.
Atherosclerosis 1991 Feb
PMID:Active cholesterol biosynthesis in cultured aortic smooth muscle cells: evolution during the life-span of the culture. 187 7

Cholesterol efflux was studied in cultured Ob1771 adipose cells after preloading with LDL cholesterol. Exposure to particles containing apo AII (LpAI) and particles containing apo AI and apo AII (LpAI:AII) isolated from native human plasma, and from HDL2 or HDL3, showed that only LpAI were able to promote cholesterol efflux, despite the fact that both kinds of particles were able to bind to receptor sites within the same range of concentrations (apparent Kd values between 10 and 25 micrograms/ml). During this long-term exposure, LpAI:AII demonstrated a concentration-dependent inhibition (10-60 micrograms/ml) of LpAI-mediated cholesterol efflux from adipose cells under conditions where LpAI:AII did not deliver cholesterol to the cells and where no net change in the distribution of apo AI between LpAI and LpAI:AII was observed. The antagonizing and modulating role of LpAI:AII in preventing cholesterol efflux mediated by LpAI appears not to be related to the lipid composition and cholesterol content of the particles but, rather, appears dependent upon the presence of apo AI in LpAI particles and apo AII in LpAI:AII particles. The actual concentrations of these particles in the interstitial fluid bathing peripheral cells might be critical for the in vivo occurrence of cholesterol efflux.
Atherosclerosis 1991 Apr
PMID:Differential role of apolipoprotein AI-containing particles in cholesterol efflux from adipose cells. 190 13


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