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

The studies reported here, coupled with our previous studies, indicate that LDL is ingested by cultured human fibroblasts in a process that resembles adsorptive endocytosis. The critical step is the binding of the lipoprotein to a high-affinity cell surface receptor. Uptake of LDL by this receptor-mediated process permits the cell to aquire cholesterol from the lipoprotein, and this acquisition, in turn, suppresses the cell's own cholesterol synthesis and activates the cell's system for reesterification and storage of the incoming cholesterol. In cells from patients with the receptor-negative form of homozygous FH, the cell surface receptor is functionally absent. The absence of high-affinity binding to this receptor produces a defective uptake of LDL and prevents the normal process of feedback regulation of cholesterol synthesis by the lipoprotein. The physiologic importance of the LDL pathway is indicated by the fact that patients who lack the LDL receptor (FH homozygotes) develop both profound hyper-cholesterolemia and fulminant atherosclerosis. It is likely that other defects in the LDL pathway account for other forms of hypercholesterolemia and atherosclerosis in man.
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PMID:The low-density lipoprotein pathway in human fibroblasts: relation between cell surface receptor binding and endocytosis of low-density lipoprotein. 18 67

The composition of very low density lipoproteins (VLDL: d less than 1.019) of New Zealand male rabbits reciving cholesterol (2 g/day) and metformin (135 mg/kg/day) is investigated. These rabbits, while showing only a slight reduction of plasma cholesterol levels, as compared to cholesterol-fed (h.c.) animals, show a marked decrease of the aortic cholesterol esters and atheromatous process. VLDL from the cholesterol + metformin group (h.c. + met), as compared to the h.c. animals, are homogenous in size and not separable into VLDL-1 and VLDL-2 subfractions by Sepharose 4B chromatography. These findings are confirmed by electron microscopy, which shows homogeneity of particle size, as well a decreased tendency of h.c. + met VLDL to aggregate. Chemical composition of h.c. + met VLDL is characterized by increased triglycerides and phospholipids, while the percentage of cholesterol esters is not significantly decreased. Phospholipid distribution of h.c. + met VLDL shows a significant decrease of sphingomyelin and increased phosphatidylinositol, the latter both as compared to h.c. and control VLDL. Apoprotein pattern of h.c. + met VLDL in polyacrylamide gels shows a relative increase of peptides with C mobility and a decrease of proteins corresponding to the arg-rich peptides. These findings exemplify a case of altered lipoprotein composition and decreased atheromatosis, in the presence of marked hypercholesteremia.
Atherosclerosis 1977 Jan
PMID:Metaformin: an antiatherosclerotic agent modifying very low density lipoproteins in rabbits. 18 80

Dogs maintained for 1 year on a semisynthetic diet containing hydrogenated coconut oil and cholesterol developed hypercholesterolemia. In those cases where plasma cholesterol levels exceeded 750 mg/100 ml, the animals also developed severe atherosclerosis. This atherogenic hyperlipoproteinemia was characterized by the presence of beta very low density lipoproteins (B-VLDL), increased levels of low density lipoproteins (LDL), and the occurrence of the HDLc lipoproteins. In all of these cholesterol-rich lipoproteins the arginine-rich apoprotein (ARP) was prominent. Moreover, the HDLc (d = 1.006-1.02) contained the ARP as the only detectable apoprotein. The atherosclerosis involved the abdominal aorta, coronary and cerebrovascular arteries, and many of the peripheral arteries. Histologically, the aortic lesions were characterized by a variable intimal proliferative response and extensive medial lipid deposition. In the peripheral, coronary, and cerebral arteries, the lesions were more extensive and involved primarily the media of the vessel wall, with little intimal reaction in many cases. The correlation between the in vivo disease process and the response of aortic smooth muscle cells (SMC) grown in tissue culture to the various cholesterol-induced lipoproteins was examined. B-VLDL, LDL, and HDLc (but not HDL2) caused a marked accumulation of free and esterified cholesterol in the SMC. The cholesterol accumulation was found to be more extensive in canine SMC than in swine smooth muscle cells or smooth muscle cells of other species in response to a similar lipoprotein cholesterol concentration. The enhanced sterol uptake appeared to be a property of canine smooth muscle cells rather than a property of the canine lipoproteins. These in vitro results may be related to the observed propensity for the development of medical disease that was demonstrated in the in vivo studies.
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PMID:Canine hyperlipoproteinemia and atherosclerosis. Accumulation of lipid by aortic medial cells in vivo and in vitro. 19 82

The effect of different lipoproteins (lipoprotein-X and lipoprotein-B; LP-X and LP-B) on hepatic cholesterol synthesis was studied in vivo in rats. Lipoproteins were continuously infused into rats for 16 hours so that 24 mg cholesterol/100 g body weight were applied. Serum cholesterol level was nearly doubled after the infusion period. Lipoprotein electrophoresis revealed the predominance of the infused lipoprotein in the serum. LP-B infusion caused a reduction of cholesterol synthesis (42% of control values) and reduced the increased cholesterol synthesis of bile fistula rats to values below normal. LP-X did not reduce hepatic cholesterol synthesis significantly nor did it normalize the enhanced synthesis following biliary diversion. However, hepatic free cholesterol concentration increased after LP-X infusion. The effect of LP-X on liver cholesterol synthesis is similar to that of lecithin: cholesterol dispersions. The failure of LP-X to exert a feedback inhibition on cholesterol synthesis may therefore contribute to the mechanism of hypercholesterolemia in obstructive jaundice.
Atherosclerosis 1977 Apr
PMID:Effect of lipoprotein-X on hepatic cholesterol synthesis. 19 23

The author studied the influence of testosterone metabolite--5alpha-androstan-3beta,17beta-diol--on the development of hyperlipidemia and atherosclerosis in chinchilla rabbits given cholesterol-free semisynthetic atherogenic diet. The metabolite under study inhibited the development of hypercholesterolemia and hyperbetalipoproteinemia and decreased blood phospholipid content in the blood serum of experimental animals below the initial level. Lipid content in the sum total fraction of pre-beta and beta-lipoproteins decreased under the effect of the mentioned metabolite; there was also a fall in the amount of lipoproteins of low density and their greater saturation with cholesterol. Development of experimental atherosclerosis was intensified.
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PMID:[Effect of 5alpha-androstan-3beta, 17beta-diol on serum lipids and lipoproteins and the development of experimental atherosclerosis]. 19 69

Hypercholesterolemia caused a decrease in the activity of adenylcyclase in rabbit liver tissue and in thrombocytes; hypertriglyceridemia, which developed after administration of hydrocortisone, led to an increase in the activity of adenylcyclase and in the content of 3,5-AMP in adipose tissue. Activities of adenylcyclase, phosphodiesterase and content of prostaglandines E1 and F2alpha were measured in thrombocytes of 39 healthy men without any symptoms of of ischemic heart impairment, in 52 patients with coronary atherosclerosis of the III degree (by Myasnikov's classification) as well as in 12 patients during the period of rehabilitation after myocardial infarction. The activity of adenylate cyclase system was impaired in atherosclerosis. This phenomenon might be caused by alteration in concentration of glucocorticoids in the organism.
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PMID:[Cyclic adenosine monophosphate and atherogenic factors]. 20 91

Recent investigations on cholesterol metabolism in man have led to new insights into diseases associated with abnormal accumulations of cholesterol in plasma (hypercholesterolemia), arterial tissues (atherosclerosis) and biliary tract (gallstones). Regulation of cholesterol synthesis under the influence of dietary and plasma cholesterol, may play a crucial role in determining biliary and tissue concentrations of this sterol. Plasma concentrations, on the other hand, appear to be controlled by complex mechanisms for secretion, transformation and removal of plasma lipoproteins. The recent identification of specific cellular receptors for uptake of plasma lipoproteins represents a significant advance for the understanding of regulation of both plasma and tissue concentrations, and possibly of the basic mechanisms underlying accumulation of cholesterol in atherosclerotic plaques.
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PMID:Cholesterol metabolism in man. 20 11

In order to develop a tolerance to experimental atherosclerosis newborn rabbits were immunized with various fractions of atherogenic lipoproteins (lipoproteins of low density, lipoproteins of very low density and total fraction of these lipoproteins), isolated from blood serum of adult rabbits with experimental hypercholesterolemia. The tolerance to atherosclerosis proved to be achieved in immunization with lipoproteins of very low density. The lesser effect was observed using the total fraction of lipoproteins. The tolerance was not developed in immunization with lipoproteins of low density.
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PMID:[Nature of the lipoprotein antigen responsible for the development of resistance to experimental atherosclerosis following its use in immunization of newborn rabbits]. 20 95

A simple procedure has been devised to give virtually pure preparations of polymorphonuclear leucocytes. This has permitted study of the regulation of cholesterol biosynthesis at cell level. Freshly isolated cells from donors with various forms of hyperlipoproteinaemia have been shown to have very low levels of cholesterol synthesis, presumably due to high circulating levels of apoprotein-B in donor plasma [1]. The activity of the rate-limiting enzyme for cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, rapidly increases as the cells are incubated in lipoprotein-deficient medium, until, by 12 h, cells from patients heterozygous for familial type IIa hypercholesterolaemia are clearly distinguished from other hyperlipoproteinaemias. The possible significance of this finding is discussed in relation to the causation and treatment of atherosclerotic disease.
Atherosclerosis 1978 Mar
PMID:Regulation of cholesterol synthesis in the hyperlipoproteinaemias. Polymorphonuclear leucocyte abnormality specific to familial type II hypercholesterolaemia. 20 84

BR-931 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio-(N-beta-hydroxyethyl)-acetamide], a new hypolipidemic agent of low toxicity, was evaluated in several tests of lipolysis and hyperlipidemia in rats, and in the cholesterol-induced atherosclerosis in rabbits. Significant hypolipidemic activity was observed in rats with doses of the agent at 12.5--50 mg/kg. In the Triton-induced hyperlipidemia, 50 mg BR-931 per kg was equieffective as 200 mg of clofibrate (CPIB) per kg. In contrast with CPIB, BR-931 exerted a powerful antilipolytic activity against epinephrine, ACTH, nicotine and cold exposure. BR-931 was particularly effective in diet-induced hyperlipidemias. Ethanol lipemia was totally prevented by the agent at 100 mg/kg. With Nath's diet, doses as low as 25 mg/kg significantly reduced hypercholesterolemia and hypertriglyceridemia. In these last two tests, the distribution of lipoprotein cholesterol was also determined. CPIB did not affect HDL cholesterol levels that had been decreased by the diets; in contrast, BR-931, already at doses of 50 mg/kg, brought the HDL/total cholesterol ratio back toward normal. A significant HDL cholesterol increase, together with some reduction of atheromatosis, was also observed in cholesterol-fed rabbits. BR-931, a potent inducer of liver peroxisones and of mitochondrial carmitine acetyltransferase, appears to be a hypolipidemic agent of high efficacy and low toxicity for the clinical treatment of hyperlipidemias and atherosclerosis.
Atherosclerosis 1978 May
PMID:Pharmacological profile of BR-931, a new hypolipidemic agent that increases high-density lipoproteins. 20 96


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