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)

In vitro cholesteryl synthesis from oleic acid [1-14C] was studied with enzyme preparations from human thoracic aorta and liver. Results from studies on the properties of the esterifying system provide good evidence that the mechanism involves fatty acyl-CoA-cholesterol acyl transferase. In studies on human thoracic aorta with varying degrees of atherosclerotic disease, and pairs of normal and diseased aorta from the same subject, there was no obvious relationship between aortic cholesteryl esterifying activity and severity of atheroma. Normal aorta from two young males, presumably free of atherosclerosis, had relatively very low esterifying activity. In the six liver samples tested, there was negligible esterifying activity, in contrast to the high activity seen in the case of rat liver. For the thin layer chromatographic isolation of the labeled cholesteryl oleate a solvent system of isooctane:diethyl ether (100:6) was found to give a better separation of the ester than the petroleum ether: diethylether:acetic acid system generally used.
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PMID:Studies on cholesterol esterification in human tissues. 2 46

We have postulated that the accelerated snythesis of cholesteryl ester in atherosclerotic microsomes may result in part from decreased acyl-CoA hydrolase activity in arterial tissue, because acyl-CoA is a common substrate for both reactions. We have now investigated the influence of nutritional status, type of diet, and diabetes on the acyl-CoA hydrolase activity of otherwise normal aortic microsomes. Fasting rabbits for 16 hr diminished the acyl-CoA hydrolase activity approximately 30%. The activity of this aortic microsomal enzyme in rats maintained on a high-carbohydrate diet for 5 weeks was comparable to the activity observed on a high fat (olive oil) diet. The type of fat in the diet influences the acyl-CoA hydrolase activity: oils containing 77% oleic acid (high-oleic safflower oil) and containing 70% linoleic acid (conventional safflower oil) lowered the aortic microsomal acyl-CoA hydrolase activity in comparison to a more saturated fat (cocoa butter). Aortic preparations of rats made diabetic by streptozotocin exhibited higher acyl-CoA hydrolase activity than the normal. The results show that conditions associated with human atherogenesis (diabetes and saturated fat diet) increase rather than suppress the activity of this arterial enzyme in normal arterial tissues of the rat.
Atherosclerosis 1977 Mar
PMID:Influence of dietary status and diabetes on aortic acyl-CoA hydrolase activity. 13 97

Increase of acyl-CoA synthesis was observed when extracts of rat arterial wall were incubated with pantetheine [D-bis-(N-pantothenyl-beta-aminoethyl)-disulfide]. Cholesteryl ester synthesis from palmitate in the arterial wall extract in vitro was higher with arteries from rats on high cholesterol diet than with those from rats on normal diet, but the synthesis was reduced in the arteries of rats on high cholesterol diet with pantetheine. Triglyceride synthesis was higher with arterial wall extracts of rats on high cholesterol diet than with preparations from rats on normal diet and was not reduced with those of rats on high cholesterol diet plus pantetheine. The value of the effects of pantetheine on lipid metabolism in the prevention of atherosclerosis is pointed out.
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PMID:Effects of pantetheine on cholesteryl ester synthesis in the arterial wall of rats on high cholesterol diet. 48 3

beta-Oxidation of long-chain fatty acids increases many-fold in atherosclerotic aortas; this may be due to an increase in the activity of the mitochondrial enzyme hexadecanoyl-CoA: carnitine O-hexadecanoyltransferase EC 2.3.1.23 (trivial name: carnitine palmitoyltransferase, CPT). To investigate this possibility, an assay for arterial CPT was developed and used to measure CPT activity in mitochondrial fractions isolated from aortas of rabbits fed high-fat (HF) or high-fat plus cholesterol (HFC) supplemented diets. The arterial CPT assay was linear with respect to mitochondrial protein between 0.03 and 0.30 mg and assay time between 3 and 12 min. Maximum CPT activity was observed at concentrations of palmitoyl-CoA between 5 and 25 micron, higher concentrations of palmitoyl-CoA inhibited CPT activity. CPT activity was measured in mitochondrial fractions isolated from aortas of rabbits fed the HFC-supplemented diet for up to 48 days. No visible lesions were observed in aortas of rabbits fed HFC-diet for 3,9, or 21 days, however, by 48 days atheromatous lesions covered in excess of 60% of the intimal surface of the aorta. No lesions were visually observed in aortas of rabbits receiving the HF-diet. Despite the development of gross atherosclerotic lesions, there were no changes in CPT activity observed that could account for a dramatic increase in fatty acid oxidation. It is concluded that the increase in beta-oxidation of long-chain fatty acids in atherosclerosis is not attributable to an increase in CPT activity.
Atherosclerosis 1979 Sep
PMID:Carnitine palmitoyltransferase activity in mitochondrial fractions isolated from aortas of rabbits fed cholesterol-supplemented diets. 49 40

A study was undertaken to test the hypothesis that an abnormally high concentration of acyl-CoA:cholesterol acyltransferase in atherosclerotic microsomes is partly responsible for augmented esterification of cholesterol. We approached the problem indirectly by measuring the incorporation of radioactivity into cholesteryl ester from [1-14C]palmityl-CoA in normal microsomes after enrichment of their concentration of microsomal free cholesterol to levels characteristic of atherosclerotic microsomes. Elevation of free cholesterol content induced increased cholesterol esterification approximately linearly over the range studied. The cholesterol-esterifying activity of atherosclerotic microsomes was not greater than that of normal microsomes having the same concentration of cholesterol. The results suggest that, with acyl-CoA constant, augmented cholesterol esterification in atherosclerotic microsomes is an effect of high microsomal cholesterol concentrations and not due to an increase in the concentration of the enzyme.
Atherosclerosis 1977 Dec
PMID:Studies of the mechanism of augmented synthesis of cholesteryl ester in atherosclerotic rabbit aortic microsomes. 59 52

Large dietary intakes of yogurt are found to lower cholestermia in man. This effect is associated with a reduction of incorporation of radioacetate into serum cholesterol. The effect appears slowly and persists after intake of the yogurt stops suggesting that the mechanism involves the synthesis of a regulatory protein rather than an allosteric effect. The effective agent is postulated to be hydroxymethyl glutarate which inhibits the regulatory enzyme hydroxymethyl glutaryl CoA reductase (EC 1.1.1.3.4).
Atherosclerosis 1977 Mar
PMID:A factor in yogurt which lowers cholesteremia in man. 84 78

Chronic administration of ethyl 2-methyl-2(4-chlorophenoxy)-propionate [clofibrate, CPIB], ethyl 6-cyclohexylchroman-2carboxylate, and ethyl 6-phenylchroman-2-carboxylate to normolipemic rats, in vivo, reduced serum cholesterol levels and inhibitid the activiry of hepatic 3-hydroxy-3methyl-glutaryl Coenzyme A. Only clofibrate was found to lower liver cholesterol content after pretreatment for 4 or 18 days. The cyclic analogs, ethyl 6-cholorochromone-2-carboxylate and 9-chloro-2,3-dihydro-5H-1,4-dioxepino [6,5-b] benzofuran were inaffective as cholesterol lowering agents in normolipemic rats. These findings indicate that appropriate modification of clofibrate can lead to the development of compounds which are selective and equally effective to clofibrate as potential hypocholesterolemic agents. Results obtained in these studies are also discussed in terms of the known structural requirements of biological activity for this series of cyclic analogs in the Triton WR-1339 hyperlipemic rat model and modes of action of the parent compound.
Atherosclerosis 1977 May
PMID:Comparison of hypocholesterolemic activity for cyclic analogs of clofibrate in normolipemic rats. 85 13

The effect of cholesterol feeding and estrogen administration on synthesis of fatty acids in liver mitochondria, microsomes and cytoplasm of male rabbits has been investigated. The synthesis was measured by the incorporation of [1(-14)C] acetyl CoA or [2(-14)C]malonyl CoA into long chain fatty acids under optimal conditions. It was found that atherogenesis markedly decreased the fatty acid synthesis in cytoplasm. The mitochondrial fatty acid synthesis was not affected by the disease. There was a small but measurable decrease in the synthesis of fatty acids in microsomes. Estrogen had no effect on the synthesis of fatty acids in mitochondria or microsomes. But if effectively counteracted, after a short lag period, the decreased synthesis of cytoplasmic fatty acids observed in atherosclerosis. It is possible that liver fatty acid synthetase is one of the enzyme systems through which estrogens exert their atherosclerosis-retarding effect. The decreased cytoplasmic fatty acid synthesis observed in atherosclerosis might account for the low levels of saturated fatty acids reported in liver and plasma lipids of atherosclerotic animals.
Atherosclerosis 1977 Aug
PMID:Effect of cholesterol feeding and estrogen treatment on synthesis of fatty acids in liver. 88 99

Cholesterol esterification in the arterial wall was investigated with cell-free preparations of intima-media from control rabbits and rabbits rendered atherosclerotic by feeding a diet containing 1% cholesterol. In the presence of 2 mM ATP and 0.1 mM CoA, the major activity for esterification of [4-14C] cholesterol added in vitro was found in the 12,000 g and 105,000 g pellets. In control animals, the activity in the latter pellet was twice that in the former. After cholesterol-feeding for 6 months, the activity increased 5-fold in the 105,000 g pellet and 2-fold in the 12,000 g pellet of the atherosclerotic intima-media. Prostaglandin E2 (PGE2) in concentrations between 2 and 12 X 10(-7) M exhibited a dose-dependent inhibition of the esterifying activity in both particulate preparations. The inhibition was 97% at PGE2 concentrations greater than 1.2 X 10(-6) M in preparations from control animals. Inhibition by PGE2 in preparations from atherosclerotic rabbits was also observed. These results suggest a possible regulatory role of PGE2 in cholesterol esterification in the arterial wall.
Atherosclerosis 1977 Jun
PMID:Inhibition of cholesterol esterification in rabbit aorta by prostaglandin E2. 90 19

The activity of fatty acyl CoA synthetase and fatty acyl CoA:cholesterol acyltransferase was determined in microsomal fractions from normal and atherosclerotic rabbit aortic tissue. No change in fatty acyl CoA synthetase activity was observed as a result of cholesterol feeding in contrast to the several-fold increase in the activity of fatty acyl CoA:cholesterol acyltransferase seen in atherosclerotic tissue. Inhibition of both enzymes was observed when clofibrate, or the tetrahydronapthyl analog of this drug were added in vitro. The inhibitory effects were most pronounced on the fatty acyl CoA:cholesterol acyltransferase.
Atherosclerosis
PMID:Fatty acyl CoA synthetase activity in normal and atherosclerotic rabbit aortic tissue. 120 Nov 48


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