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 oxygen and glucose uptake, lactate formation, ATP/ADP and NADH/NAD ratios and incorporation of [14C]acetate and [14C]linolenic acid into lipids of early fatty streaks and more advanced complicated atherosclerotic lesions of human aorta were determined during aerobic and hypoxic incubation. Compared with grossly normal appearing sections of the aorta in intima and media preparations of early fatty streaks the oxygen uptake was increased while that in further developed atheroma was slightly diminished. Under aerobic incubation conditions the metabolic state of fatty streaks and atheroma was characterized by increased lactate formation, NADH/NAD ratio and incorporation of [14C]acetate and [14C]linolenic acid into the lipids, but by a lowered ATP/ADP ratio. More pronounced changes in these metabolic parameters were observed when the aortic tissue segments were incubated under hypoxic conditions. The analysis by argentation TLC of fatty acid methylesters derived from total lipids of aerobically incubated fatty streaks revealed an increased incorporation of [14C]acetate into the highly unsaturated long-chain fatty acids. In developed atherosclerotic lesions and in hypoxia the incorporation of radioacetate into the polyunsaturated fatty acids and the formation of 20:4 fatty acid from [14C]linolenic acid were, in contrast to the above finding, decreased while the synthesis of eicosatrienoic acid was increased. This finding suggests a block in the desaturation step of linoleic into 20:4 fatty acid in further developed atheroma and in hypoxia. In aerobically incubated atherosclerotic lesions and in hypoxia the palmitic acid was synthesized mainly by chain elongation while in grossly normal areas of the aorta at least part of this acid was synthesized de novo.
Atherosclerosis 1976 Sep
PMID:Comparative studies on fatty acid synthesis in atherosclerotic and hypoxic human aorta. 18 99

The lipoproteins have been examined in more than 300 serum or plasma samples taken during life or at post mortem from a fairly wide range of mammals, birds and reptiles. The material, which was collected over a period of several years, was subjected to a limited range of lipid analyses, but all specimens were submitted to electrophoresis with paper or cellulose acetate membrane as supporting medium. The lipoprotein pattern in mammals appears to be basically similar to that in man, but there are wide variations in lipid concentrations; the highest levels being found in bears, seals and primates. High concentrations were also observed in many birds and a few reptiles, but the lipoprotein patterns in these vertebrates differ from those in mammals and are further greatly modified by oviparity. Semi-quantitative data on the degree of atherosclerosis were available on the animals that died. There was only a crude positive correlation between the intensity of the arterial disease and high serum beta-lipoprotein levels, and it was concluded that the latter are probably of only secondary importance in the development of spontaneous atherosclerosis in animals.
Atherosclerosis 1976 Oct
PMID:Serum lipoproteins and atherosclerosis in animals. 18 81

A number of agents including a series of 1,3-bis (substituted phenoxy)-2-propanones were screened in vitro for their ability to inhibit hepatic and intestinal microsomal sn-glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase. Effective inhibitors reduced in vivo hepatic and intestinal glycerolipid production and with one exception also lowered serum triglyceride levels, suggesting that agents which inhibit potential rate-limiting steps of glycerolipid biosynthesis may be effective hypolipidemic agents. Two compounds, 1-methyl-4-piperidyl bis (p-chlorophenoxy) acetate (Sah 42-348) and 1,3-bis (p-methylphenoxy)-2-propanone were the best inhibitors of glycerolipid biosynthesis and lipid-lowering agents. The lipid-altering effects of both drugs were compared to chlorophenoxyisobutyrate during high fructose intake in rats. Each agent reduced fructose induced glycerolipid biosynthesis and serum triglyceride levels to similar degrees.
Atherosclerosis 1977 Jun
PMID:Hypolipidemic activity of in vitro inhibitors of hepatic and intestinal sn-glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase. 19 74

Sterol synthesis from radioactive acetate and the suppression of this synthesis by human low density lipoprotein (LDL) have been investigated in skin fibroblast strains derived from infant donors and from donors over the age of 70 years. The activity of the enzyme hydroxymethylglutaryl-CoA reductase and its repression by LDL has also been investigated in these fibroblast strains and in senescent cells of the foetal lung cell strain MRC-5. No age-related differences could be detected either in repression of [3H]acetate incorporation by LDL, or in repression of HMG-CoA reductase activity.
Atherosclerosis 1979 Jul
PMID:Regulation of cholesterol synthesis in skin fibroblasts derived from old people. 22 8

From experimental work, an influence of a drug with hypolipidemic and hypouricemic acition on blood coagulability and platelet function may be expected. Consequently, if these effects were demonstrable in man the drug could be assumed to reduce the tendency to develop thrombosis and atherosclerosis in patients with hyperlipidemia and hyperuricemia. In the study reported, the effect of 2-acetamidoethyl-(p-chlorophenyl)-(m-trifluoro-methylphenoxy)-acetate (halofenate) was investigated in 14 patients suffering from hyperlipoproteinemia type IV and hyperuricemia. Platelet aggregation and adhesiveness, plasma levels of triglycerides, cholesterol, uric acid, and clotting factors were regularly examined during a three-month double blind trial. While uric acid and triglyceride levels decreased, no influence of the drug treatment could be observed on platelet function and blood coagulability by the laboratory methods used.
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PMID:[Effect of halofenate on triglyceride and uric acid levels, coagulation and platelet behaviour in patients with hyperlipoproteinemia type IV and hyperuricemia (author's transl)]. 22 20

The effects of the novel fenfluramine derivative, S 1204 (meta-trifluoromethyl phenyl-1 [beta(sulfamyl-3'-chloro-4'-benzoyloxyethyl)]amino-2-propane) were studied on lipid metabolism in rabbit aorta and other tissues. Pretreatment of rabbits with S 1204 (50 mg/kg orally) for 10 days strongly inhibited the aortic incorporation of an intravenous 20 muCi tracer-dose of [4-(14)C]-cholesterol given 24 h earlier. However, incorporation of such cholesterol radioactivity into the liver, intestine, lung or plasma was not affected, in comparison with control animals. One hour after i.v. injection of a 100 muCi tracer-dose of [2-(14)C]acetate, S 1204 significantly reduced the radioactivity of total lipids in the aorta and liver. Such inhibition of acetate incorporation into arterial lipids was observed with all lipid fractions (that is, free fatty acids, esterified cholesterol, especially phospholipids, glycerides and free cholesterol). Incorporation of acetate into intestinal triglyceride fractions was also significantly decreased. The results indicate that S 1204 may have anti-atherogenic properties, which could be valuable in the clinical treatment of atherosclerosis.
Atherosclerosis 1979 Mar
PMID:The effect of a putative anti-atherosclerotic agent (S 1204) on lipid metabolism in rabbit aorta. 46 17

Two preparations active in reducing hepatic cholesterol biosynthesis were isolated from bovine skim milk. One of the inhibitors was in the dialysate and was identified as orotic acid (OA). The other inhibitor, present in the retentate, was not identified. Orotic acid appears to act by inhibiting cholesterol biosynthesis before the formation of mevalonate, whereas the retentate inhibitor exerts its effect beyond the formation of mevalonate in the biosynthetic pathway. Human milk also inhibited the incorporation of both labeled acetate and mevalonate into cholesterol by rat liver. Orotic acid was not detectable in human milk samples employed in this study. Administration of [6-14C]orotate to rats revealed its conversion to uracil in the liver. Subsequent work demonstrated that uracil had inhibitory activity on hepatic cholesterol biosynthesis similar to that of orotate when incubated with rat liver slices.
Atherosclerosis 1979 Apr
PMID:Effect of milk constituents on hepatic cholesterol-genesis. 46 19

Activity of microsomal enzymes and the patterns of cholesterol metabolism were studied in mice of WSR/y strain, characterized by spontaneous development of atherosclerosis within the later periods of life, after early postnatal administration of an inductor of the enzymes 3-acetate-16 alpha-isothiocyanopregnenolone (ATCP). Administration of ATCP into newborn mice of SWR/y strain, from the 2nd up to 16th day after birth, led to a stable increase in activity of arylhydrocarbonate hydroxylase (an enzyme participating in unspecific metabolism of drugs), which was observed during the whole experimental period (4 months). The treatment with ATCP caused also a distinct increase in activity of cholesterol-7 alpha-hydroxylase (a key enzyme of cholesterol biotransformation and elimination) as well as a considerable decrease in content of cholesterol and lipoprotein atherogenic fractions in blood serum. The rate of cholesterol biosynthesis was similar both in mice treated with ATCP and in the control animals.
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PMID:[Effect of the early postnatal induction of microsomal enzymes on their activity and the cholesterol content in the blood of adult mice from a hypercholesteremic line]. 47 88

The metabolic effects of an acute acetate load have been investigated in chronic uremic patients and in controls. The decay rate of blood acetate levels was significantly lower in patients than in controls. Higher levels of blood acetoacetate and 2-oxoglutarate and plasma triglycerides were observed in the patients after the load. No difference was detectable in plasma levels of unesterified fatty acids and cholesterol between the two groups of subjects. Acetate oxidation in citric acid cycle may be reduced in uremia owing to a lack of coenzyme A. These observations raise the possibility that chronic acetate administration with the dialysate induces hypertriglyceridemia and accelerates the development of atherosclerosis in hemodialysis patients.
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PMID:Acetate intolerance in chronic uremic patients. 50 62


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