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)

Lipogenesis was measured with glucose-2-(14)C and acetate-1-(14)C in the everted aortas of normal and atherosclerotic rabbits. More glucose-2-(14)C than acetate-1-(14)C was incorporated into lipids in both the normal and the atherosclerotic aorta. Radiocarbon from glucose-2-(14)C appeared mainly in triglycerides and phospholipids with a small amount in cholesteryl esters. Incorporation increased almost threefold with atherosclerosis, most of the radioactivity being in the glycerol moiety; radioactivity was predominantly in carbon 2 of glycerol. About 70% of the acetate-1-(14)C incorporated into phospholipids and triglycerides was in the fatty acids, and the remainder was in glyceride-glycerol; 98% of the radioactivity in cholesteryl esters was in the fatty acid moiety. Incorporation into cholesteryl esters was increased most during the development of atherosclerosis. Fatty acid synthesis was similar from both acetate-1-(14)C and the 2 carbon unit derived from glucose-2-(14)C, viz., predominantly de novo synthesis of fatty acids with 14 and 16 carbon atoms, and elongation for those of 18 carbons and longer.
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PMID:Lipogenesis from glucose-2- 14 C and acetate-1- 14 C in aorta. 512 36

Mevinolin inhibited the incorporation of [14C]acetate into cholesterol by human monocyte-derived macrophages (HMD macrophages) when both mevinolin and [14C]acetate were added simultaneously to the culture medium. Longer incubation with mevinolin, 24 h, led to a marked increase in the degradation of [125I]low density lipoprotein (LDL) via the high affinity receptor for LDL by HMD macrophages. Furthermore, this increased LDL receptor activity in cells incubated for 24 h with mevinolin and lipoprotein-depleted serum (LPDS) led to a nearly 3-fold increase in the formation of cholesteryl esters when these cells were then incubated with LDL for 24 h. Continuous exposure to mevinolin did not result in a constant increase in LDL receptor activity. Cells exposed to mevinolin for 24 h on day 3 had increased LDL receptor activity, but continuous exposure to mevinolin with 5% human serum (HS) from day 3-9 resulted in degradation of [125I]LDL at the same rate as observed in cells incubated with 5% HS alone. Cholesterol synthesis from [14C]acetate was decreased in cells incubated for 24 h in 5% HS + mevinolin compared with 5% HS alone, and in 10% LPDS + mevinolin compared with 10% LPDS alone; however, cells incubated with LPDS + mevinolin synthesized cholesterol at higher rates than did cells cultured in 5% HS alone. Continuous culture with 5% HS + mevinolin for 5 days resulted in cholesterol synthesis at control levels. These data show that following inhibition of cholesterol synthesis by mevinolin, HMD macrophages maintain cholesterol homeostasis by increasing LDL receptor activity to obtain cholesterol from LDL.
Atherosclerosis 1984 Jul
PMID:Inhibition of cholesterol synthesis by mevinolin stimulates low density lipoprotein receptor activity in human monocyte-derived macrophages. 608 38

21 women (mean age 60 years, range 48-72) were given depot medroxyprogesterone acetate (DMPA), 1,000 mg/week parenterally for 6 months, as part of the treatment for endometrial carcinoma in either clinical stage I or II. Before treatment and after 1, 3 and 6 months of treatment serum apolipoprotein AI was analyzed by electroimmunoassay. There was a significant decrease in apolipoprotein AI after the administration of DMPA, compared to the value before treatment. A low level of apolipoprotein AI is considered a risk factor for the development of atherosclerosis and cardiovascular disease. Such a risk might therefore be anticipated if the period of treatment was extended to several years.
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PMID:Changes in apolipoprotein AI after treatment with high-dose medroxyprogesterone acetate. 623 58

The rates of cholesterol synthesis from acetate were studied in freshly isolated peripheral blood lymphocytes in 41 age- and sex-matched subjects with essentially normal serum lipid profiles. Insulin binding to erythrocytes obtained from the same blood samples was also studied simultaneously. From the data on lymphocyte cholesterol synthesis in the absence or presence of low density lipoprotein in the medium, an index, LDL50, was calculated for each subject. This is the concentration of LDL cholesterol (nmol/ml) in the medium necessary to reduce cholesterol synthesis to 50% of that in the absence of LDL. On the basis of LDL50, the subjects could be segregated into three distinct groups, I, II, and III, with LDL50 of 6.5, 23.3, and 77.0 nmol/ml, respectively. This grouping was independent of the serum lipid profiles, age or sex. Insulin binding studies showed that the amount of insulin specifically bound and the number of insulin receptors per cell were inversely correlated with LDL50. LDL50 was also determined for 4 subjects with clinically manifested consequences of familial hypercholesterolemia. The LDL50 values for these individuals corresponded to values obtained for subjects in group III. The number of insulin receptors and the amount of insulin bound in these patients were correspondingly low. These results suggest that LDL50 may be useful in discerning abnormal cellular cholesterol metabolism in subjects with or without accompanying hyperlipidemias.
Atherosclerosis 1983 Dec
PMID:Differential suppression of lymphocyte cholesterol synthesis by low density lipoprotein and erythrocyte insulin receptors in normolipidemic subjects. 636 80

Vervet monkeys ( Ceropithecus aethiops pygerethrus ) were placed on semipurified diets containing 14% fat of which 3.2 or 6.0% was present as trans-unsaturated fatty acid (t-FA). Two groups were fed the high and low levels of t-FA for a year and two others were fed t-FA for 6 months and then returned to the control diet for 6 months more. One other group was fed the control diet for a year. The control diet contained 14% fat which was a mixture of 72% olive oil and 28% corn oil. There were no significant differences in weight gain. Monkeys fed 6% t-FA or control diets for one year had lowest liver weights. Serum cholesterol and triglycerides in monkeys fed 3.2% t-FA for one year were 134 and 55 mg/dl, respectively; in monkeys returned to control diet after 6 months on 6% t-FA the values were 146 and 50 g/dl. Serum and triglyceride levels for the other 3 groups were 166 +/- 2 and 70 +/- 2 mg/dl. Liver cholesterol levels ranged from 4.0 mg/g (3.2% t-FA) to 4.7 mg/g (control) and 4.8 mg/g (6% t-FA). Lecithin:cholesterol acyltransferase (LCAT) activity was 59.0 microM/h for controls and ranged from 52.4 microM/h (3.2% t-FA) to 73.4 microM/h (6% t-FA). Cholesterol synthesis by liver slices was not affected by diet when the substrate was acetate. When mevalonate was used, the monkeys fed either level of t-FA for 12 months exhibited greatly reduced (about 80%) cholesterogenesis. The levels of t-FA in serum and liver reflected the amount in the diet. After being returned to control diet levels of t-FA in serum and liver of monkeys (fed 3.2% t-FA) fell by 97 and 94%, respectively, and those in serum and liver of monkeys fed 6% t-FA fell by 65 and 91%. There were no significant differences in aortic atherosclerosis or arteriosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)
Atherosclerosis 1984 Apr
PMID:Effect of trans-unsaturated fats on experimental atherosclerosis in vervet monkeys. 642 84

Chromium ions (Cr3+)evoked a biphasic curve of changes of rat liver microsomal cholesterol biosynthesis using [14C]acetate and/or [14C]mevalonate as precursors. While for the lower range of Cr3+ concentrations the rate of cholesterol biosynthesis rises, at concentrations above 8 X 10(-6) M they evoke a decrease in the cholesterol biosynthesis, up to 50% down on its control value at a concentration of 8 X 10(-4) M. Differences were more pronounced when using [14C]mevalonate instead of [14C]acetate as precursor. The activity of the microsomal enzyme biphenyl-4-hydroxylase showed an equally intense rise to that of cholesterol biosynthesis up to a 8 X 10(-6) M Cr3+ concentration. Above this concentration, however, the activity of the enzyme starts to drop. NADPH-cytochrome c reductase and NADPH-oxidase were decreased at all Cr3+ concentrations used, which cover a 100-fold range. Lineweaver-Burk plots of the cytoplasmic glucose-6-phosphate dehydrogenase demonstrated an uncompetitive mechanism of inhibition by Cr3+ ions. The results are discussed in terms of the possible significance of the Cr3+ concentration-dependent effects on cholesterol biosynthesis, with the observed atherosclerosis in Cr-deficient humans.
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PMID:Rat liver microsomal cholesterol biosynthesis and drug oxidase activity are affected by chromium ions (Cr3+) in vitro. 643 2

In 23 women who had used the injectable contraceptive depot medroxyprogesterone acetate (DMPA) for at least 1 year, the mean serum high-density lipoprotein cholesterol (HDL-C) level was distinctly lower than in 23 women carrying an IUD. The high serum DMPA levels during the 1st few weeks after a subsequent DMPA injection, and the low levels 12 weeks after the injection were found to be associated with the same (low) serum HDL-C level. For this reason, a fall in the serum HDL-C level in DMPA users is probably not a direct effect of the DMPA, but rather an indirect effect of the diminished production of endogenous estrogens in the ovaries of DMPA users. Though the investigation does not justify definite conclusions, it appears advisable not to prescribe DMPA to women with an increased risk of atherosclerosis and myocardial infarction. (author's)
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PMID:[Injectable contraceptive, DMPA, serum HDL cholesterol and heart infarct]. 645 21

Two progestins with different androgenic activity were compared for their effects on plasma high density lipoproteins and postheparin plasma lipase activities in premenopausal women. Levonorgestrel, a nortestosterone-derived steroid with androgenic activity reduced plasma HDL cholesterol by 17% (P less than 0.05) and HDL2 cholesterol by 30% (P less than 0.05), without changing the HDL3 cholesterol concentration. At the same time the postheparin plasma hepatic lipase activity was increased by 56% (P less than 0.01) whereas the lipoprotein lipase was not changed. None of these effects was reproduced during administration of medroxyprogesterone acetate, a progestin with low androgenic activity. The results suggest, first, that the decrease of HDL cholesterol observed during treatment with progestins is related to the androgenic activity of the steroid used, and, second, that the change in HDL (HDL2) is caused by androgen-induced increase of hepatic lipase activity.
Atherosclerosis
PMID:Different effects of two progestins on plasma high density lipoprotein (HDL2) and postheparin plasma hepatic lipase activity. 646 May 9

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

Bovine milk contains two inhibitors of hepatic cholesterol genesis. One of these, identified as orotic acid, influences the early segment of the cholesterol biosynthetic pathway and suppresses the conversion of acetate to mevalonate. In this study the other inhibitor was shown to curtail the formation of compounds past farnesyl pyrophosphate on the squalene-cholesterol branch of the pathway. Thus cholesterol synthesis may be suppressed while the production of two other products of the branched pathway, dolichol and ubiquinone, is allowed to continue. The possible role of these ingested regulators in the metabolism of the young until they achieve sufficient development is discussed.
Atherosclerosis 1983 Dec
PMID:The modulating effect of an inhibitor of cholesterolgenesis present in bovine milk upon the synthesis of cholesterol, dolichol and ubiquinone. 666 Dec 67


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