Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholesterol ester-loaded J774 macrophages attached to microcarrier beads were perfused or incubated with lipoproteins in vitro. Cholesterol influx was reduced by decreasing LDL cholesterol, efflux was promoted by increasing HDL cholesterol or by adding apolipoprotein A-I/phosphatidylcholine complexes to the perfusate or incubation medium. Addition of sera obtained from patients after LDL apheresis or plasma exchange resulted in much smaller increments in cell cholesterol than pretreatment sera, due to decreased influx, but efflux was unchanged despite the reduction in HDL cholesterol by plasma exchange. These data suggest that extracorporeal cholesterol removal promotes mobilization of intracellular cholesterol ester mainly by reducing cholesterol influx.
Atherosclerosis 1991 Jun
PMID:Cholesterol flux in cholesterol ester-loaded macrophages in an in vitro perfusion system. 190 65

Small-diameter vascular grafts woven from bioresorbable lactide/glycolide copolymers have been successfully interposed into aortas of normal NZW rabbits. The current study examines the histologic and functional reactions to these bioresorbable grafts in severely hypercholesterolemic rabbits, a standard animal model of atherosclerosis. Sixty rabbits were placed on a 2% cholesterol, 6% peanut oil atherogenic diet. Baseline serum cholesterols and triglycerides were measured and repeated at operation 3 months later. Woven polyglactin 910 (PG910) grafts were interposed into infrarenal aortas. Fifty-two rabbits died on the diet or within 3 days of surgery and eight survived operation (normal NZW rabbit operative mortality is less than 10%). Cholesterol levels rose from 63 to 1989, p less than .001. Of the eight survivors, five died after 3 weeks, and one died after 2 1/2 months. Two were sacrificed at 2 and 4 months. Four aortic disruptions with retroperitoneal hematomas, one pseudoaneurysm, and one diffuse aneurysm were observed, greater than in normal rabbits, p less than .001. Inspection revealed severe atherosclerosis. Histologically, 3-week explants showed only small areas of neointima with myofibroblasts and endothelial cells; the outer capsules were infiltrated by lipid-laden macrophages. Graft material in 2- to 4-month explants was replaced by tissue with histologic atherosclerosis. More severe atherosclerosis was observed in native aortas at the perianastomotic areas than the more distant aortic segments. Abundant intracellular lipid was seen also in splenic histiocytes and hepatic cells with evidence of micronodular cirrhosis. Macrophages phagocytizing bioresorbable prostheses may release growth factors mediating the formation of a cellular tissue conduit. Severe hypercholesterolemia may alter monokine release from macrophages resulting in a weakened prosthesis/tissue complex.
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PMID:Effects of hypercholesterolemia on healing of vascular grafts. 191 76

Sitosterolemia and xanthomatosis are characterized by the development of tendon and tuberous xanthomas at an early age and premature atherosclerosis despite normal plasma cholesterol concentrations. The reason(s) for the xanthoma formation and premature atherosclerosis are not clearly understood. The accumulation of sitosterol in the tissues of these patients could be due to increased uptake of low density lipoprotein (LDL) via LDL receptors because of an expanded sitosterol pool caused by sluggish turnover and decreased excretion of sitosterol into bile and feces coupled with the hyperabsorption of sitosterol. We have studied sitosterol and cholesterol turnovers, the biliary and fecal excretion of neutral and acidic steroids, and the response of plasma sterol (sitosterol and cholesterol) levels to either a sterol-free formula or low plant sterol diet in three patients. The average half-life of the first exponential (tA1/2) for sitosterol was 9.2 +/- 3.3 (mean +/- SD) days, which was more than twice that in normal humans. The second exponential (tB1/2) was 156 +/- 108 days, which was nearly 10 times longer than that for normal humans. The average cholesterol production rate in pool A was 0.87 g/day, which is about 40% of that in normal humans. Cholesterol synthesis measured by the sterol balance technique was also found to be about 70% lower than that for normal humans. In two patients fed a sterol-free formula diet, by 25 days their plasma sitosterol and cholesterol levels had decreased by 42% and 36%, respectively. However, in one patient plasma sitosterol and cholesterol concentrations remained unchanged while on the low plant sterol-mixed food diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis. 191 14

Cardiovascular disease remains the major cause of death in the industrialized world with dyslipidemia, hypertension and cigarette smoking leading a long list of risk factors. Recently, controversy arose from some critical articles expressing concern about the evaluation and interpretation of statistical data of epidemiologic studies. One study using covariance analysis reported an absence of the widely accepted negative association between coronary heart disease (CHD) and high density lipoprotein (HDL) cholesterol. Also criticism was expressed regarding the cost-effectiveness of preventive measures such as the use of lipid lowering drugs on life expectancy. Because of such recent scientific controversy and discussions already taking place in the media, we have summarized in this article recent epidemiologic evidence including a meta-analysis of the major epidemiologic studies on HDL. We have directed particular attention to 3 large epidemiological studies, i.e., the Familial Atherosclerosis Treatment Study (FATS), the Program on the Surgical Control of the Hyperlipidemias (POSCH), and the Cholesterol Lowering Atherosclerosis Study (CLAS), all of which have clearly demonstrated a desirable effect of intensive lipid lowering therapy on coronary lesions.
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PMID:[Risk factors for coronary heart disease]. 194 9

1. Young goats were used to study factors contributing to atherosclerosis. 2. Cholesterol in egg yolk affected plasma cholesterol concentration more than did a similar amount of crystalline cholesterol in the diet. 3. Goats fed high fat diets developed fatty lesions in their aortas. 4. Cholesterol concentration in low-density lipoprotein was greatest in goats fed restricted-calorie diets without exercise, but least in goats fed liberally and exercised. 5. Cholesterol concentration in liver and fat deposition in aorta were greatest in the restricted-calorie, no exercise regime.
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PMID:The domestic goat: a useful model to determine effects of diet and exercise on cholesterol accumulation in the body. 196 22

The 2-year therapy effect on femoral atherosclerosis was evaluated in the Cholesterol Lowering Atherosclerosis Study (CLAS), a randomized, placebo-plus-diet-controlled angiographic trial of colestipol-niacin therapy plus diet in men with previous coronary bypass surgery. Different diet compositions were prescribed to enhance the differential in blood cholesterol responses between the two groups. The annual rate of change in computer-estimated atherosclerosis (CEA), a measure of lumen abnormality, was evaluated between treatment groups. A significant per-segment therapy effect was found in segments with moderately severe atherosclerosis (p less than 0.04) and in proximal segments (p less than 0.02). When segmental CEA measures were combined into a per-patient score using an adaptation of the National Heart, Lung, and Blood Institute scoring procedure, a significant therapy effect was observed (p less than 0.02). Total variance of the annual change rate in CEA was as predicted from pilot studies, but measurement variation was larger. The therapy effect observed in femoral arteries, although significant, was less marked than the strong and consistent benefit previously reported for both native coronary arteries and aortocoronary bypass grafts.
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PMID:Effects of colestipol-niacin therapy on human femoral atherosclerosis. 199 86

Evidence has been accumulating that insulin has actions that may promote the development of atherosclerosis. Research has involved three broad areas: actions of insulin on cultured arterial cells, the effect of insulin on isolated artery preparations, and the development of lipid-containing lesions in the arteries of experimental animals. Insulin, in concentrations similar to those found in physiologic conditions, stimulates proliferation of cultured arterial smooth muscle cells from a number of species, including humans. Insulin also stimulates migration of smooth muscle cells. Cholesterol synthesis and low-density lipoprotein interaction with its receptor in smooth muscle cells are stimulated by insulin. Insulin's mitogenic action appears to be mediated by the insulin-like growth factor receptor. Endothelial cells cultured from large vessels are resistant to the actions of insulin, but hyperglycemia inhibits their proliferation. Insulin deficiency protects animals from experimental atherosclerosis; this protection is lost with insulin treatment. Insulin administration results in lipid-containing lesions in chickens and rats fed a normal diet, and in increased lipid synthesis in the arteries of pigs and dogs. Isolated artery preparations from insulin-deficient or insulin-treated animals undergo lipid metabolism at a rate that correlates with the insulin concentrations in the donor animals. The biological actions of insulin (and glucose) on arterial tissue suggest that hyperglycemia and hyperinsulinemia may promote the development of atherosclerosis.
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PMID:Insulin as a mitogenic factor: role in the pathogenesis of cardiovascular disease. 199 20

The Cholesterol Lowering Atherosclerosis Study, a randomized, angiographic clinical trial, has demonstrated the beneficial effect of niacin/colestipol therapy on coronary and femoral atherosclerosis. The primary outcome was a panel-determined consensus score evaluating global coronary changes determined angiographically at 2 years. This article presents an evaluation of interreader agreement in independently assessing the status of native coronary arteries and overall coronary condition. Parameters include 1) identification of the presence of lesions and lesion changes; 2) estimation of lesion severity (percent stenosis) and amount of change in lesion severity; and 3) global assessment of change in coronary status. Readers independently agreed on 1) presence of lesions (82%) and change in lesions (51%); 2) percent stenosis +/- 10% (76%) and change in stenosis +/- 10% (81%); and 3) global assessment of change in coronary status within one step (96%). Results of these analyses may be useful in effectively designing angiographic trials that use a panel of human evaluators as well as computerized methods for angiographic interpretation.
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PMID:Evaluation of human panelists in assessing coronary atherosclerosis. 199 56

Cholesterol atheroembolisation is increasingly encountered as a complication of cardiac catheterisation. We report three cases seen recently in our unit. Autopsy and histological evidence confirmed cholesterol atheroembolism in one case, while the other two patients presented with classical clinical features of this condition. All three patients were elderly with extensive atheromatous disease. No excessive difficulty was encountered at catheterisation. Embolisation involved the gastrointestinal tract, the skin and extremities, and the kidneys. Despite anticoagulation, dialysis and surgical intervention all our patients died. With investigative and therapeutic catheterisation being increasingly performed in the setting of severe atherosclerosis, the need for continued scrutiny for catheter-induced complications is emphasised.
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PMID:Cholesterol atheroembolism: an increasingly frequent complication of cardiac catheterisation. 200 56

Phenotypic consequences of ras oncogene expression were studied in cells conditionally transformed by T24 H-ras and a temperature-sensitive SV40 large T antigen (tsA58). Previous studies have demonstrated that transformation of REF52 cells by ras and SV40 large T antigen requires continuous T antigen expression. Thus, tsA58/T24 H-ras transformants ceased growing when transferred to a restrictive temperature for T antigen expression. Inhibition of cell growth was accompanied by massive accumulations of cholesterol esters, triglycerides and a third lipid species, identified as glycerol ethers on the basis of mobility on TLC. Cholesterol esters were derived from serum lipoproteins, and appeared to accumulate because LDL receptor expression and activity did not decline in growth arrested cells. Triglycerides and glycerol ethers were products of cell metabolism. The process lacked features characteristic of adipocyte differentiation, but may suggest mechanisms important in diseases, such as atherosclerosis, that involve abnormal accumulations of neutral lipids. Accumulating lipid species may also include metabolites induced by ras that accumulate in growth-arrested cells.
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PMID:Massive accumulation of neutral lipids in cells conditionally transformed by an activated H-ras oncogene. 200 Feb 21


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