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)

Plasma cholesterol was lower in spontaneously hypertensive rats (SHR), while plasma triglyceride and free fatty acid were increased in comparison with control normotensive Wistar-Kyoto (WK) rats. Correspondingly, [1-14C]-acetate incorporation into liver cholesterol was clearly decreased in SHR as compared with WK. As for lipogenic enzyme activities, glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase in SHR were respectively decreased, increased and not significantly different, in comparison with WK rats. Liver cholesterol was rather low and cardiac triglyceride was slightly increased in SHR. Aortic cholesterol and triglyceride levels were not significantly different between SHR AND WK rats. Thus, SHR have an abnormality in lipid metabolism, especially in cholesterol synthesis, but the pathological implication of this in hypertension and related vascular lesions is not yet clear.
Atherosclerosis 1977 Nov
PMID:Lipid metabolism in spontaneously hypertensive rats (SHR). 2 30

The effects of different doses of clofibrate and gemfibrozil on liver size, serum triglyceride concentration and the activities of hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and carnitine acyltransferases were studied in male rats. Both clofibrate and gemfibrozil treatment effectively decreased the fructose-induced hypertriglyceridaemia and increased the liver to body weight ratio. Clofibrate treatment also induced an increase of many times in the activities of mitochondrial alpha-GPD and carnitine acyltransferases, the effect increasing with the dose used. The effect of gemfibrozil on the activities of the enzymes was significantly smaller. There was no correlation between the decrease in serum triglyceride concentration and the changes in the activities of the enzymes. Only clofibrate increased the rate of fatty acylcarnitine oxidation in isolated mitochondria. It is concluded that both drugs increased the size of the rat liver, but that only clofibrate influenced the mitochondrial enzyme activities of mitochondrial carnitine acyltransferases and the accelerated mitochondrial oxidation of fatty acids are not the mechanisms by which these drugs lower serum lipid levels.
Atherosclerosis 1979 Jan
PMID:Effect of clofibrate and gemfibrozil on the activities of mitochondrial carnitine acyltransferases in rat liver. Dose--response relations. 46 13

Rats were maintained for 2 weeks on 3 different diets; a basal diet, one containing 0.1% cholate, and one containing 0.1% cholesterol and 0.1% cholate. Each dietary group was further divided into subgroups whose diet contained 0, 5 or 10% (dry weight) of minced corbicula (Corbicula japonica Prime). Feeding corbicula significantly reduced the increase of cholesterol levels in rats fed the cholesterol diet. Though corbicula contains several sterols, sterols other than cholesterol were almost not absorbed. Serum and liver triglyceride levels were significantly reduced by feeding corbicula meat in all the dietary groups. Activities of glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase were also markedly reduced by feeding corbicula. The results suggest that corbicula is a hypolipidemic food.
Atherosclerosis 1979 Sep
PMID:Effect of feeding the shell fish (Corbicula japonica) on lipid metabolism in the rat. 49 41

Differences in the ratio of molecular forms of crystalline glycerol-3-phosphate dehydrogenase (GPD, EC 1.1.1.8) from sceletal muscle and in their primary structure were found in rabbits with experimental atherosclerosis as compared with normal animals. In atherosclerosis the molecular weight of GPD and of its fragments was increased; the amino acid composition of these GPD molecules differs from that of control rabbits as shown by estimation of content of 8 amino acids. Experimental atherosclerosis is apparently related to alteration in the GPD primary structure.
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PMID:[Structure of cytoplasmic glycerol-3-phosphate dehydrogenase in experimental atherosclerosis in rabbits]. 59 98

The fibrous plaque is regarded as the vascular lesion most characteristic of atherosclerosis. The notion that these lesions develop from mural thrombi has received considerable support, and there is also much support for the idea that plaques form as a reaction to mechanical or chemical damage to the endothelium. As an alternative to these two hypotheses, Benditt and Benditt have suggested that plaques represent monoclonal proliferation of altered smooth muscle cells similar to leiomyomas. Evidence in favor of this suggestion has been obtained using tissues from human black females who are heterozygous for the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD). In such individuals, as a result of random inactivation of the X-chromosome during embryogenesis, all normal tissues contain both the A and B isoenzymes of G6PD, when assayed electrophoretically, whereas plaques and other lesions suspected of being of monoclonal origin contain predominantly one isoenzyme. A certain proportion of fatty streaks also show a single G6PD isoenzyme pattern, suggesting that some fatty streaks act as the foreunners of the fibrous plaque.
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PMID:The human atherosclerotic plaque. 84 15

The main objective of the study was to investigate the effect of the calcium antagonists Verapamil (2 mg.kg-1.day) and Nifedipine (1 mg.kg-1.day-1) on cholesterol (1%) induced atherosclerosis in rabbits. The drugs were administered s.c. twice daily over a period of 8 weeks. Blood lipid levels were determined three times during the experiment. After the experimental period the animals were killed and macroscopic changes on the aorta were recorded. For histochemical investigation samples were taken from the arch of the aorta and coronary artery. In cryostat sections lipids were determined by Sudan black B and Fett rot 7 B and the following enzymes were assayed: acid phosphatase, non-specific and acid esterase, acid beta-galactosidase, dipeptidyl peptidase I and II, and glucose-6-phosphate dehydrogenase. Following treatment with the calcium antagonists the levels of triacylglycerols and of total cholesterol were significantly increased in comparison with the control and diet groups. The ratio of HDL cholesterol to total cholesterol decreased in the treated animals. In lipoid plaques the activity of enzymes was enhanced in all experimental animals. There were however no qualitative differences in the composition of plaques between individual groups, which exhibited only quantitative differences. The number of migrating macrophages was increased only in the nifedipine treated animals. The extent of plaques was significantly decreased after nifedipine treatment, whereas verapamil failed to exert antiatherogenic effect. (Tab. 2, Fig. 4, Ref. 22.).
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PMID:[The effect of verapamil and nifedipine on the development of experimental atherosclerosis in rabbits]. 152 79

Dehydroepiandrosterone (DHEA) is an endogenous steroid that blocks carcinogenesis, retards aging, and exerts antiproliferative properties. In vitro, it is a potent inhibitor of glucose-6-phosphate dehydrogenase, the first committed step of the pentose phosphate pathway. In man, serum levels of DHEA and its sulfate peak in early adulthood and drop markedly with age. Epidemiologic evidence indicates that low levels of DHEA or its sulfate conjugate are linked to an increased risk of developing cancer or of death from cardiovascular disease. Like cancer, atherosclerosis is a proliferative process characterized by both initiation and promotion phases. This similarity provided a framework in which to study the antiatherogenic effects of DHEA. Rabbits were randomly assigned to four groups. Two groups of rabbits received aortic endothelial injury by balloon catheter and were fed a 2% cholesterol diet for 12 wk. DHEA, 0.5%, was incorporated into the diet of one group receiving the 2% cholesterol diet and endothelial injury and also into the diet of one of the control groups. Animals were killed after 12 wk and aortas, hearts, and livers were studied. Plasma samples were analyzed for total cholesterol, VLDL, LDL, HDL, triglycerides, DHEA, and DHEA-sulfate levels. The atherogenic insult resulted in severe atherosclerosis in animals not treated with DHEA. In those receiving DHEA there was an almost 50% reduction in plaque size (P = 0.006), inversely related to the serum level of DHEA attained. Fatty infiltration of the heart and liver were also markedly reduced. These beneficial actions were not attributable to differences in body weight gain, food intake, total plasma cholesterol or distribution of cholesterol among the VLDL, LDL, or HDL fractions. The results show that high levels of plasma DHEA inhibit the development of atherosclerosis and they provide an important experimental link to the epidemiologic studies correlating low DHEA-sulfate plasma levels with an enhanced risk of cardiovascular mortality.
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PMID:Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury. 296 22

Prolonged exposure of rats to cigarette smoke resulted in significant alterations in the metabolism of lipids. There was a significant increase in the concentration of cholesterol, triglycerides and phospholipids in most of the tissues, particularly the heart, aorta and lungs. Cholesterol, triglycerides and phospholipids decreased in the serum HDL and increased in LDL + VLDL. There was increased cholesterogenesis in the heart, lungs and liver, as evidenced by increased activity of HMG-CoA reductase and increased incorporation of labelled acetate into cholesterol. Incorporation of label into the triglycerides also increased in these tissues. Activity of lipoprotein lipase in the extrahepatic tissues was decreased. Activity of glucose-6-phosphate dehydrogenase and malic enzyme increased in the heart and lungs. There was decreased concentration of bile acids in the liver.
Atherosclerosis 1988 Apr
PMID:Effect of exposure of rats to cigarette smoke on the metabolism of lipids. 336 90

The clonal nature of atherosclerotic plaques has been examined in diet-induced atherosclerosis of interspecies hybrid hare females (Lepus timidus (female) X Lepus europaeus (male], which exhibit genetic mosaicism with respect to glucose-6-phosphate dehydrogenase (G6P-D). Four diet groups have been used: control pellet diet, hyperlipemic (HL) diet, and HL diet supplemented with two different concentrations of 25-hydroxycholesterol. Lesion and nonlesion tissue samples and primary cultures developed from similar samples were used to determine the G6P-D variant patterns. A close correlation was observed, using regression analysis, between the in vivo and the in vitro phenotype. As has been reported earlier by us, most lesions in this animal model were heterozygous and the few homozygous areas recorded were all in the diet groups supplemented with 25-hydroxycholesterol. However, in tissue culture, homozygosity appeared with greater frequency, still of the T phenotype. In order to rule out maternal dominance as a factor, preliminary experiments involving G6P-D analysis have been carried out using tissue samples and cell cultures derived from a reverse cross. These also show a strong bias toward the T phenotype. The studies presented here highlight the difficulties in interpretation using G6P-D analysis as the sole criterion to determine the clonal nature of the atherosclerotic plaques. It also seems likely that the kind of diet given to induce atherosclerosis might influence the nature of the clonal growth. Studies using transfection are essential to determine whether transforming sequences are present in atherosclerotic lesions.
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PMID:Clonal nature of atherosclerotic plaques. 337 61

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


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