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)

The accumulation of cholesterol esters in foam cells of the arterial intima is an important characteristic of fatty streak lesions of atherosclerosis. We wished to know if cholesterol ester accumulations in cells could be mobilized by altering their external milieu. Thus, phospholipid dispersions were used to remove cholesterol from a cholesterol ester-enriched cell line. Rat hepatoma cells, Fu5AH, were loaded with cholesterol esters by incubation in medium supplemented with hyperlipemic rabbit serum. After removing the loading medium, we incubated the cells in serum-free medium containing egg phosphatidylcholine dispersions. Unesterified cellular cholesterol level decreased in the first 4 h and then remained at a constant level. The cholesterol esters decreased after a lag time of about 2 h and the triacylglycerol level increased after 3 h. The decrease in cellular cholesterol ester depended on the amount of phospholipid in the medium. Cellular cholesterol ester decreased with increasing concentration of medium phospholipid to 2 mumols/ml and then plateaued. The removed cellular sterols appeared in the medium as free cholesterol. Since there was no measurable cholesterol esterase activity in the medium, the cholesterol ester in the cells was hydrolyzed before it appeared in the medium. The fatty acyl composition of the cellular cholesterol esters remained unchanged after significant reduction, suggesting that the hydrolysis of cholesterol esters was not specific for the acyl chain. Sphingomyelin and dimyristoyl phosphatidylcholine dispersions, though cytotoxic, were also effective in reducing cellular cholesterol esters. These experiments demonstrate that cholesterol ester accumulations in these cells can be reduced when phospholipid dispersions are used as cholesterol acceptors in the extracellular medium.
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PMID:Mobilization of cholesterol from cholesterol ester-enriched tissue culture cells by phospholipid dispersions. 706 56

The activity of cholesterol ester hydrolase was measured in subcellular fractions from rat and pigeon aortas using a glycerol-dispersed cholesterol oleate substrate preparation. The specific activity of acid cholesterol ester hydrolase (assayed at pH 5) in adventitia tissue fractions was 40-50 fold greater than in media-intima fractions from rat aorta. Soluble and particulate subcellular fractions from rat aorta (media-intima) were observed to have cholesterol ester hydrolase activity with both an acid (pH 4.5-5) and a neutral (pH 7.5) pH optimum. A comparison of the subcellular distribution of acid cholesterol ester hydrolase with the lysosomal marker enzyme, N-acetylglucosaminidase, suggests that the acid hydrolase activity originated in aortic lysosomes; the neutral cholesterol ester hydrolase was predominantly soluble. Acid and neutral cholesterol ester hydrolases could also be distinguished on the basic of the effects of Mg Cl2 and NaCl on hydrolase activity and on rates of thermal denaturation. Both acid an neutral hydrolases from rat aorta (media-intima) were inhibited by chloroquine (half-maximal at 2-4 mM), and both hydrolases were characterized as having the same apparent affinity for the glycerol-dispersed cholesterol oleate substrate. Acid and neutral cholesterol ester hydrolases were also observed in preparations from pigeon aortas. The specific activity for both acid and neutral hydrolases was higher in atherosclerosis-susceptible White Carneau pigeon aortas in comparison to Show Racer pigeon aortas.
Atherosclerosis 1982 Jan
PMID:Properties of acid and neutral cholesterol ester hydrolases in rat and pigeon aortas. 707 88

Arteriosclerotic lesions were formed in rat aorta by the administration of vitamin D2, a high-fat diet and a thyroid suppressing agent. This treatment increased the serum total cholesterol level to 12 times the control level. In the arteriosclerotic lesions that were induced the activities of lysosomal enzymes, such as acid phosphatase and acid lipase, were higher than in controls, that of acid cholesterol esterase was decreased, those of microsomal lipid-synthesizing enzymes--such as acyl-CoA synthetase and cholesterol ester synthesizing activity--were increased and that of neutral cholesterol esterase was decreased. These data suggest that lipid metabolism in arteriosclerotic lesions was changed, resulting in the accumulation of cholesterol esters in the aorta. Administration of high-fat diet and thyroid suppressing agent also increased the serum cholesterol levels to 12-fold the control level, but did not induce arteriosclerotic lesions. After this treatment the activities of hydrolyzing enzymes, such as acid and neutral cholesterol esterase and lipase, in the aorta increased, but the activities of lipid synthesizing enzymes also increased. These data suggest that lipid metabolism in the aorta in this condition changed to compensate for the large influx of serum lipids and to prevent arteriosclerosis. The roles of the serum lipid level, cell injury and lipid metabolism in the aorta in forming arteriosclerotic lesions are discussed on the basis of these results.
Atherosclerosis 1982 May
PMID:Lipid metabolism in arteriosclerotic arterial wall of rats. 709 82

Sex differences in aortic cholesterol esterase activity and changes in the activity following castration and gonadal hormone treatment were investigated in rats. Differences in the enzyme activity were apparent after 2.5 months and became most significant after 6 months. The activity in the aorta and the liver was significantly higher in female rats. Prepubertal orchiectomy increased the aortic activity, feminizing the type of metabolism, whereas postpubertal orchiectomy, and both pre- and postpubertal ovariectomy induced no change in the activity. The administration of testosterone to female rats significantly decreased the aortic activity, masculinizing the type of metabolism. However, the administration of testosterone or of 17 beta-estradiol to male rats had no effect. These results suggest (1) that there are clear sex differences in aortic cholesterol esterase activity, (2) that prepubertal exposure to androgens plays a critical role in the sexual differentiation in aortic and hepatic cholesterol ester metabolism, and (3) that the administration of testosterone can temporarily masculinize the type of metabolism. These results partly explain the sexual differences in susceptibility to atherosclerosis.
Atherosclerosis 1982 Jun
PMID:Sex differences in aortic cholesterol esterase activity in rats, and changes of the activity following castration and gonadal hormone treatment. 711 69

Bezafibrate markedly reduced the activity of fatty acyl CoA:cholesterol acyltransferase (ACAT) in the microsomal fraction of aortas from cholesterol-fed rabbits, while clofibrate was a less potent inhibitor. The activity of lysosomal cholesterol ester hydrolase (LCEH) was not significantly affected by either agent, indicating that inhibition of ACAT rather than stimulation of LCEH is a mechanism whereby these agents may decrease the cholesterol ester content of atherosclerotic aorta.
Atherosclerosis 1982 Oct
PMID:The effect of bezafibrate and clofibrate on microsomal ACAT and lysosomal cholesterol ester hydrolase activity in the cholesterol-fed rabbit aorta. 715 86

The characteristics and properties of lipid metabolism in the aorta and the brain microvessels of rabbits were investigated to clarify the role of lipid metabolism in formation of atherosclerosis. In rabbit aorta, cholesterol esterase and lipase each had an acidic and a neutral optimum pH, whereas acyl-CoA synthetase, acyl-CoA: cholesterol acyltransferase, triglyceride synthesizing activity and choline phosphotransferase each had one neutral optimum pH. These pH optima were similar to those in rats. High cholesterol diet induced atheromatous lesions in the aorta, but not in the brain microvessels. In atheromatous aorta, the acid lipase and acid phosphatase activities were higher than in controls, but not the acid cholesterol esterase activity. Moreover the activities of neutral lipase, acyl-CoA synthetase, acyl-CoA:cholesterol acyltransferase, triglyceride synthesis and choline phosphotransferase were increased, but neutral cholesterol esterase activity was normal. These data suggest that lipis metabolism in the atheromatous aorta is changed in a manner favoring accumulation of lipids, especially cholesterol esters. In controls, most of the above enzyme activities in the brain microvessels were higher than those in the aorta. However, these enzyme activities in the brain microvessels were not changed by cholesterol feeding. Thus it is suggested that the properties of lipid metabolism in the aorta and brain microvessels, including permeability of lipoproteins into the vessel walls, are important in formation of atherosclerosis in addition to the serum factors.
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PMID:Lipid metabolism in the aorta and the brain microvessels of rabbits on high cholesterol diet. 718 94

Non-specific esterase (NSE) activity has been studied by light and electron microscopic enzyme histochemistry in lesion and non-lesion areas of swine abdominal aortas in a sequential study of the regression of atherosclerosis. On the light microscope level, no activity was demonstrable in normal artery but in atherosclerotic lesions it was seen in round cells, elongate cells and foamy cells. Ultrahistochemistry identified these reactive cells as macrophages, smooth muscle cells and foam cells of undetermined origin. Since NSE has been shown to hydrolyze cholesteryl oleate, it is possible that histochemical demonstration of NSE activity may be, in part, localization of cholesteryl ester hydrolase activity.
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PMID:Non-specific esterase activity during regression of swine aortic atherosclerosis. 721 21

Acid cholesteryl ester hydrolase (CEH) activity was assayed in mononuclear cells of patients with symptomatic atherosclerosis (transient ischemic attacks, TIA) and in age-matched controls showing no evidence of atherosclerosis. The acid CEH level of TIA patients was significantly lower than that of controls (1074 +/- 128 vs 2113 +/- 255 pmol/mg P/hr, mean +/- SE). Neither mononuclear cell nor plasma cholesterol and cholesteryl ester concentrations differed significantly between atherosclerotic and control groups. TIA women had lower mononuclear cell concentrations of free cholesterol than men.
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PMID:Cholesteryl ester hydrolase activity in human symptomatic atherosclerosis. 721 70

In spontaneously hypertensive rats, prolonged hypertension caused a decrease in aortic cholesterol esterase activity with N-acetyl-beta-D-glucosaminidase activity increased and acid phosphatase activity unchanged [3]. The present study was undertaken to compare these changes with those caused by other experimentally induced types of hypertension. Treatment with DOCA-salt for one month significantly elevated both aortic cholesterol esterase and acid phosphatase activities. In contrast, to spontaneous hypertension, venous changes were also observed. An intake of 1% NaCl ad libitum produced results similar to those with the DOCA-salt treatment, despite the fact that blood pressure did not increase. This suggested that humoral factors were the main cause of the elevated enzyme activities in DOCA-salt hypertension. In rats made hypertensive by unilateral renal arterial constriction with contralateral nephrectomy (one clip--one kidney hypertension) or without contralateral nephrectomy (one clip--two kidney hypertension), aortic cholesterol esterase activities were unchanged, while aortic N-acetyl-beta-D-glucosaminidase, and aortic and venous acid phosphatase activities were increased. These results show distinct differences in the response of lysosomal enzymes during the three hypertensive states.
Atherosclerosis 1981 Jul
PMID:Aortic cholesterol esterase and other lysosomal enzyme activities in DOCA-salt, renal and spontaneous hypertension in the rat. 725 25

Premenopausal women, 1 control group (n=9) taking no medication or using no oral contraceptives (OCs) and 1 treated group (n=10) receiving OCs for contraception, were studied to determine any effects OCs have on mononuclear cell cholesteryl ester hydrolase (CEH) activity. 9 of the 10 medicated women were taking Ortho Novum 1/50 and the other person was receiving Norlestrin 1/50. Normally menstruating women (controls) showed a significant rise in CEH levels on Day 20 of the menstrual cycle (P .05). The enzyme activity in women on OCs was significantly lower than control women in 3 of 4 testing periods. In addition, plasma and mononuclear cell cholesterol and esters were measured along with plasma estrogen and progesterone levels. Although free cholesterol levels in normal cycling (control) women and in the OC group did not vary significantly during the menstrual cycle between the 2 groups, the women on OCs had significantly higher ester levels than the control women in 3 of the 4 test periods P .05-.005). When paired ratios of plasma cholesterol to esterified cholesterol were compared between control and OC groups, the ratio of free/esterified was significantly higher in the control group in 3 of 4 tests. In the mononuclear cells, on the other hand, the cholesterol/cholesteryl ester ratio was significantly lower in the control group during the 4 test periods. No association between levels of endogenous sex hormones (estradiol, progesterone) and CEH activity were found. CEH levels may be related to incidence of atherosclerosis, and women taking OCs may have increased chances of developing this disease.
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PMID:The effect of oral contraceptives on mononuclear cell cholesteryl ester hydrolase activity. 736 9


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