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

Cholesterol metabolism was examined in aortic smooth muscle cells from atherosclerosis-susceptible White Carneau pigeons that have been shown to lack a functional LDL receptor pathway. In cells incubated in the presence of whole serum or low density lipoprotein (LDL) the rate of cholesterol synthesis from [1-14C]acetate or of HMG-CoA reductase activity was 20-100 times greater than for mammalian cells incubated under the same conditions. Unexpectedly, cholesterol synthesis decreased by nearly 50% after preincubation for 24 hr with lipoprotein-deficient serum (LPDS). This occurred without a change in cellular cholesterol content. Neither the high rate of cholesterol synthesis nor the effect of LPDS could be accounted for by differences in cell turnover or state of growth. Cholesterol added in ethanol was ineffective in altering cellular cholesterol synthesis or esterification even though a near doubling in cellular free cholesterol content occurred. Cholesterol synthesis and esterification were, however, able to be regulated with 25-OH cholesterol and mevalonolactone, as indicated by their ability to suppress cholesterol synthesis and to stimulate cholesterol esterification. In spite of the high rate of endogenous cholesterol synthesis, cellular cholesterol content was maintained at a constant level by the efficient efflux of the newly synthesized cholesterol from the cell. Unlike mammalian cells that require a cholesterol acceptor in the medium for efflux to occur, cholesterol efflux from pigeon cells occurred in the absence of a cholesterol acceptor. This suggests either that pigeon cells utilize a different mechanism for cholesterol efflux or that they produce their own cholesterol acceptor. As a result of a lack of a functional LDL receptor pathway, pigeon smooth muscle cells do not maintain cholesterol homeostasis through the controlled uptake of exogenous LDL cholesterol, as do mammalian cells. Rather, pigeon smooth muscle cells would appear to regulate cholesterol concentrations at the level of either cholesterol synthesis or efflux.
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PMID:Cholesterol metabolism in pigeon aortic smooth muscle cells lacking a functional low density lipoprotein receptor pathway. 649 37

Hepatic beta-hydroxy-beta-methylglutaryl CoA (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase (7 alpha-hyd), and fatty acid synthetase (FAS) activities and cholesterol levels were determined in chicks fed isonitrogenous corn- and high-protein barley flour (HPBF) based diets. HMG-CoA reductase (-27%), 7 alpha-hyd (-30%), and serum cholesterol (-13%) were reduced, whereas FAS increased (28%) in comparison to a corn-based (control) diet. fractions obtained by serial extractions of HPBF with solvents of increasing polarity were fed at levels equivalent to 20% HPBF in a corn-based diet to female White Leghorn (WHL) chickens for 3 weeks. A petroleum ether-soluble fraction of HPBF produced 3 effects: an increase in body weight (18%), a strong suppression of HMG-CoA reductase (-36%) and FAS (-40%) accompanied by decreases in serum triglyceride (-9%) and cholesterol levels (-23%). The methanol-soluble fraction produced a significant suppression of HMG-CoA reductase (-49%) and serum cholesterol level (-29%), and an increase in FAS activity (95%). These effects were duplicated in 7-week-old broiler chickens which also showed a significant decrease in chol-LDL (low density lipoprotein) levels by these fractions. The factor(s) lowering serum cholesterol concentration was about equally divided between the polar and nonpolar fractions, and each was significantly more effective than the 20% HPBF in the corn-based diet. The observed effects on lipogenesis and cholesterogenesis might be attributed to a number of chemical constituents of HPBF, but cannot be attributed to the water-insoluble plant fibers.
Atherosclerosis 1984 Apr
PMID:Suppression of cholesterol biosynthesis by constituents of barley kernel. 672 4

AMO 1618 (2-isopropyl-4-dimethylamino-5-methylphenyl-1-piperidine carboxylate methyl chloride) was added to corn-soy based diets and fed to 9-week-old female chickens for 3 weeks to measure the inhibition of hepatic beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7 alpha-hydroxylase. Dose-related decreases in the activities of these two enzymes were obtained (2.5--15 ppm) of AMO 1618. Decreases in plasma total cholesterol, chol-HDL, and chol-LDL levels were observed, but the decreases in chol-LDL were substantially larger than those of chol-HDL in both chicken and rat. Assays of livers from rats fed 20 ppm AMO 1618 for 3 days had 24% less HMG-CoA reductase activity and 67% less cholesterol 7 alpha-hydroxylase activity than the controls. Plasma cholesterol in these animals was reduced 26%; the ratio of total cholesterol : chol-HDL was reduced from 3.27 to 2.67 and the chol-LDL : chol-HDL ratio was reduced from 1.96 to 1.14 as a result of the relatively brief treatment. Fatty acid synthetase (FAS) and other key lipogenic enzymes increased 1.5--4-fold in both the chicken and rat. The inhibition of HMG-CoA reductase and the induction of FAS by AMO 1618 were tested in vitro, using 10--100 micrograms (28--280 mumoles) for 15 min with isolated hepatocytes from chicken and rat. Linear responses in activity were dose-dependent and increased with duration of incubation (30 micrograms or 85 mumoles AMO 1618, 5--120 min) in both species. The results suggest the compound acts at the cellular level and AMO 1618 appears to possess several properties which recommend it for testing as a cholesterol-lowering agent in humans.
Atherosclerosis 1983 Feb
PMID:Effect of AMO 1618 on cholesterol and fatty acid metabolism in chickens and rats. 683

Mevinolin (MK-803) is a potent inhibitor of HMG-CoA reductase. After a placebo run-in period, mevinolin 5,15 or 50 mg, or placebo was given twice daily for 7-11 days under double -blind conditions ot 4 groups of 6 normocholesterolemic male volunteers. After 7 days, mean serum cholesterol fell 14%, 25% and 24% on 5, 15 and 50 mg, respectively, which was significantly greater than the fall on placebo (4%) in the case of the two higher doses (P less than 0.01). Serum triglycerides did not change significantly. Mevinolin was generally well-tolerated and there were no serious adverse effects.
Atherosclerosis 1982 Jan
PMID:Rapid and substantial lowering of human serum cholesterol by mevinolin (MK-803), an inhibitor of hydroxymethylglutaryl-coenzyme A reductase. 691 20

Regulation of the key enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase (EC: 1.1.1.34), by heterologous human lipoproteins and hormones was studied in a maintenance culture of rat hepatocytes. The liver cells were cultured under hormone and serum free conditions and maintained differentiated morphology and specific function. Under control conditions total HMG-CoA reductase increased by 50% after 24 h culture compared to 0 h values immediately after isolation. Thereafter a plateau of enzyme activity was reached lasting until 48 h, with a slight decline at 72 h. Concomitantly the "expressed" enzyme activity increased steadily, probably through dephosphorylation of latent reductase, the activation was largely complete at 48 h. During the steady state period of total reductase VLDL added to the medium at concentrations up to 50 microgram/ml protein had no effect o HMG-CoA reductase activity. In contrast, LDL suppressed the enzyme in a dose-dependent fashion to 40% of controls at 100 microgram/ml. On the other hand, HDL had the opposite effect with a significant induction up to 252% of controls at 50 microgram/ml. Insulin also caused a comparable dose-dependent stimulation of enzyme activity at 10(-8) and 10(-7)M, whereas glucagon inhibited reductase activity. Compared to the insulin action, triiodothyronine and triamcinolone prompted a minor, but still significant increase of reductase activity. Insulin and triamcinolone acted synergistically, but the combination of triamcinolone and tri-iodothyronine was only additive. All hormonal inductions of reductase could be blocked by cycloheximide. The present data establish that HMG-CoA reductase of maintenance cultured hepatocytes is subject to a complex regulation by heterologous lipoproteins as well as pancreatic, adrenal and thyroid hormones.
Atherosclerosis 1982 Jan
PMID:3-Hydroxy-3-methylglutaryl CoA reductase in cultured hepatocytes. Regulation by heterologous lipoproteins and hormones. 707 95

Either purified soya phosphatidylcholine (lecithin) or triacylglycerol (corn oil) were fed to rats on a diet containing 0.5% cholesterol. The diets contained similar amounts of linoleic acid. The effects of the two preparations on (a) serum cholesterol concentrations, (b) fatty acid profiles, (c) HMG-CoA reductase activity, (d) cholesterol absorption, and (e) faecal excretion of neutral sterols are compared. Some comparisons are also made with diets containing saturated triacylglycerol (lard) and no additional fats other than cholesterol. Serum cholesterol levels were less markedly raised on the lecithin diet, compared with the corn oil or lard diets. Evidence is presented that lecithin reduces the absorption of dietary cholesterol and also increases the excretion of neutral sterols. Our results suggest that soya lecithin is a more potent hypocholesterolaemic agent than corn oil.
Atherosclerosis 1982 Oct
PMID:A comparison of the effects of feeding linoleic acid-rich lecithin or corn oil on cholesterol absorption and metabolism in the rat. 715 91

The effects of skim milk powder (SMP) and fluid skim milk (FSM) on plasma cholesterol (CH) and hepatic liquid concentrations, and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase activity of rats of different ages were compared. Groups of young (23 days old) and older (45 days old) rats were fed a casein -based diet and provided tap water; the casein-based diet and FSM as fluid source; or tap water and the casein diet into which SMP (25% by wt.) had been isocalorically incorporated. Plasma CH concentrations were determined at 0, 1.5, 3 and 5 wk, hepatic total lipid, triglyceride and CH at 5 wk. Half of each group were killed at wk 3 and the other half at wk 5 for determinations of HMG CoA reductase activity. Both FSM and SMP decreased plasma CH levels at 1.5 and 3 wk of feeding in the young rats; plasma CH concentrations of the older rats were not altered by either FSM or SMP. Both milk derivatives increased HMG CoA reductase activity at wk 3 and wk 5 in both ages of rat, whereas hepatic lipid levels were unchanged. In these experiments the effects of feeding FSM of SMP along with a casein-based diet were comparable and included an increase in HMB CoA reductase activity, no change in hepatic lipid levels, and a decrease in plasma CH; the latter response depended on the initial age of the rat.
Atherosclerosis 1981 May
PMID:Plasma and hepatic cholesterol and hepatic HMG CoA reductase levels in rats fed fluid or powdered skim milk. 724 1

The effects of probucol treatment on cholesterol metabolism were examined in rats. Male Sprague-Dawley rats were divided into 3 groups: one group was given 0.25% probucol containing chow diet, one group was given 0.25% clofibrate containing chow diet, and the third group was fed chow diet alone. All groups of rats were maintained on these regimens for 4 weeks before killing. Probucol treatment resulted in a decrease in plasma cholesterol and cholesterol 7 alpha-hydroxylase activity. Clofibrate treatment resulted in a reduction of plasma cholesterol, hepatic HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities. The fecal excretion of neutral and acidic sterols were decreased significantly in the probucol or clofibrate-treated rats. In the bile there was a decrease in the concentration of total bile acids. These results suggest the mechanism for hypocholesterolemic action of probucol to be different from that of clofibrate.
Atherosclerosis 1980 Aug
PMID:Effect of probucol on cholesterol metabolism in the rat. 741 72

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have proven to be more effective in reducing levels of low density lipoprotein (LDL) cholesterol and to be better tolerated than other lipid-lowering compounds. Most of the trials evaluating the effects of these new agents on progression of atherosclerosis have not included individuals asymptomatic for cardiovascular disease and who have LDL cholesterol levels at or below the limits established by the National Cholesterol Education Program for initiating treatment. The Asymptomatic Carotid Artery Progression Study (ACAPS) tested the effect of the HMG-CoA reductase inhibitor, lovastatin, on early-stage carotid atherosclerosis (as detected by B-mode ultrasonography) in 919 asymptomatic men and women, 40-79 years of age, who had LDL cholesterol levels between the 60th and 90th percentiles. Participants randomized into this double-blind, placebo-controlled, factorially designed study received lovastatin (20-40 mg/day) or lovastatin-placebo and warfarin (1 mg/day), or warfarin-placebo over a 3-year period. The progression of the mean maximum intimal-medial thickness (IMT) over 12 walls of both carotid arteries represented the primary outcome. Lovastatin treatment was associated with a reduction in progression of mean maximum IMT (p < 0.001). Levels of LDL cholesterol were reduced by 28% (43.5 mg/dl [11.25 mmol/liter]) in the lovastatin group within 6 months (p < 0.0001) and remained stable throughout the follow-up period, whereas these levels remained essentially unchanged in the lovastatin-placebo group. The difference in incidence of major cardiovascular events for patients in the lovastatin-placebo group was significant: 5 versus 14, respectively (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Results of the primary outcome measure and clinical events from the Asymptomatic Carotid Artery Progression Study. 757 86

Hypercholesterolemia is common following renal transplantation and undoubtedly contributes to morbidity and mortality due to occlusive atherosclerosis in these patients. Although 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are more tolerable as low density lipoprotein cholesterol (LDL-C)-lowering agents than other classes of drugs, their use in transplant patients has been limited due to potentially serious interactions with cyclosporine. Fluvastatin is the first wholly synthetic HMG-CoA reductase inhibitor. Because it has a shorter half-life and greater protein-binding capacity than other drugs of this class and has no active circulating metabolites, fluvastatin may be safer than other HMG-CoA reductase inhibitors in this group of patients. To study this question, 19 renal transplant recipients (age, 21-70 years) with hypercholesterolemia (LDL-C > 180 mg/dL; triglycerides < 400 mg/liter) were entered into a 14-week active-treatment period with fluvastatin at 20 mg/day following dietary stabilization and a 3-week placebo washout period. Changes in LDL-C levels were compared with those obtained in control hypercholesterolemic subjects treated in the same way. The lipid-lowering ability of fluvastatin was not imparied in these patients, indicating a lack of interaction with cyclosporine. Mean liver enzyme levels, creatine phosphokinase (CPK), and creatine did not change significantly from baseline. Two subjects experienced myalgias without CPK elevations, and another subject experienced an asymptomatic increase in CPK to > 10 times the upper limit of normal, related to exercise. In conclusion, fluvastatin safely and effectively lowers elevated LDL-C levels in renal transplant recipients.
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PMID:A preliminary report of the safety and efficacy of fluvastatin for hypercholesterolemia in renal transplant patients receiving cyclosporine. 760 82


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