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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholesterol ester hydrolase activity was determined in preparations of rabbit and guinea pig aorta utilizing micellar and glycerol-dispersed cholesterol oleate substrates. Both substrate preparations demonstrated an acid pH optimum of 4--5 for the soluble and particulate rabbit media cholesterol ester hydrolase, suggesting a lysosomal origin for this activity. Approximately one-fifth of the total recovered activity was particulate. Particulate media preparations from guinea pig aorta also demonstrated cholesterol ester hydrolase activity at acid pH values with a definite optimum at pH 5 for the glycerol-dispersed substrate. However, in contrast to the rabbit media enzyme, activity was also observed at neutral pH with another optimum at pH 7. The supernatant enzyme from guinea pig media exhibited only a single pH optimum of 7. Cholesterol ester hydrolase activity from either rabbit or guinea pig media was not influenced by preincubation with cyclic AMP, ATP and protein kinase. The addition of chloroquine resulted in the inhibition of both the rabbit and guinea pig enzyme. Cholesterol ester hydrolase activity from rabbit and guinea pig media was also inhibited by phenyl methane sulfonyl fluoride; activity measured at pH 7 (guinea pig) was more sensitive to inhibition than activity measured at pH 5 (guinea pig and rabbit).
Atherosclerosis 1978 Sep
PMID:Characterization of cholesterol ester hydrolase activities in rabbit and guinea pig aortas. 3 Apr 61

Among the many, multifactorial etiologies of atherosclerosis is excessive filtration and deposition of lipids, particularly cholesterol esters, in arterial walls; furthermore, the monoclonal theory purports that the artheroma is an uncontrolled proliferation of cells similar to a benign tumor. These 2 aspects of atherosclerosis pathogenesis were studied in 5 healthy women on birth control pills by investigating the level of mononuclear cell cholesterol ester hydrolase (CEH). Control subjects underwent identical investigation. Mononuclear CEH activity was signficantly lower in women on oral contraceptives than in controls in 4 of the 5 test intervals and showed no signficant fluctuation in activity. Average value of CEH in 5 women on birth control pills was 927+ or -81 pmol/mg of protein/hour. In 5 men followed at 5-day intervals, no significant fluctuation of CEH activity was found. Mean average was 2373+ or -92. Total cholesterol and its ester in both plasma and mononuclear cells showed no signficant differences at the 5-day intervals between men and women. However, plasma cholesterol/cholesterol ester ratios were significantly higher in women than men at each of the 5-day intervals from Days 5-25. An additional link between female hormones and atherosclerosis is suggested by the finding that women on oral contracepitves, known to be predisposed to premature atherosclerosis, show reduced and nonfluctuating levels of mononuclear cell CEH.
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PMID:The effect of oral contraceptives on mononuclear cell cholesterol ester hydrolase activity in premenopausal women taking oral contraceptives: relevance to atherosclerosis. 75 88

We describe a new animal model of a genetic lipid storage disease analogous to human Wolman's disease. Affected Donryu rats, who inherited the disease in an autosomal recessive mode, manifested marked hepatosplenomegaly, lymph node enlargement, and thickened, dilated intestine. Morphologically, many characteristic foam cells were observed in livers and spleens. No adrenal calcification could be found in affected rats. Biochemical studies on spleen and liver tissues showed massive accumulation of esterified cholesterol and triglycerides, and deficiency of acid lipase for [14C]-cholesteryl oleate. This animal model could contribute greatly to the clarification of the physiological and pathological roles of lysosomal acid lipase in the metabolism of lipoproteins and cholesterol, and of the pathogenesis of atherosclerosis.
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PMID:Genetic lipid storage disease with lysosomal acid lipase deficiency in rats. 217 Jul 47

Acid cholesteryl ester hydrolase activity of mononuclear leukocytes was measured in 52 Type 2 (non-insulin-dependent) diabetic patients. Enzyme activity was significantly lower in the diabetic patients than in 14 age-matched control subjects (0.89 +/- 0.08 (mean +/- S.E.) vs. 2.20 +/- 0.17 nmol/mg protein/hr, p less than 0.01). In diabetic patients undergoing diet treatment only, the enzyme activity was significantly lower in poorly controlled patients than in well controlled patients (0.43 +/- 0.03 vs. 1.15 +/- 0.24 nmol/mg protein/hr, p less than 0.01). In the diabetic patients, there was a significant negative correlation between the enzyme activity and serum total cholesterol or low density lipoprotein cholesterol level (r = -0.361, p less than 0.01, n = 52 or r = -0.630, p less than 0.01, n = 28). These results suggest that a low level of acid cholesteryl ester hydrolase activity in mononuclear leukocyte might play an important role in the progression of atherosclerosis in Type 2 diabetes.
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PMID:Acid cholesteryl ester hydrolase activity of mononuclear leukocyte in type 2 (non-insulin-dependent) diabetic patients. 238 65

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

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

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

Cholesterol ester storage disease (CESD) is associated with premature atherosclerosis, hepatomegaly, elevated LDL cholesterol levels, and in most cases, low HDL cholesterol levels. Previous studies have shown a G-->A mutation at the 3' splice junction of exon 8 (E8SJM) of the gene encoding lysosomal acid lipase (LAL) in two kindreds with CESD. In a Canadian-Norwegian kindred with this disease, we show this mutation in conjunction with an as yet unknown T-->C transition in exon 10 predicting a Leu336-->Pro (L336P) replacement and an A-->C transversion in exon 2 predicting a T-6P replacement in the prepeptide. Identification of the L336P rather than the T-6P replacement as the second defect underlying CESD in our patient is deduced from three lines of evidence. First, the E8SJM allele is located in cis with the mutation predicting the T-6P-encoding allele but in trans with the L336P-encoding allele; second, the L336P but not the T-6P replacement cosegregates with low LAL activity in the family; third, the T-6P replacement was found in 6 of 28 alleles from subjects with normal lysosomal acid lipase activity, suggesting that this variant represents a frequent nonfunctional polymorphism. Since the residual LAL activity is higher and the clinical phenotype based on plasma lipid values and severity of hepatosplenomegaly is milder in this case than in a previously studied case who was homozygous for the E8SJM allele, we conclude that the L336P variant appears to be associated with a phenotypically mild form of CESD.
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PMID:A novel variant of lysosomal acid lipase (Leu336-->Pro) associated with acid lipase deficiency and cholesterol ester storage disease. 777 32

Multiparameter flow cytometry reveals a complex heterogeneity of mononuclear phagocyte differentiation within the peripheral blood compartment. In this study, the relation of abnormal cellular lipid metabolism to the phenotype of peripheral blood mononuclear phagocytes, which finally may be related to atherogenesis, was analyzed using recently characterized autosomal recessive defects of lysosomal acid lipase (LAL) expression as model system. The reduction of LAL activity in nine heterozygote, disease free carriers of mutations from two cholesteryl ester storage disease (CESD) pedigrees and the family of a patient with Wolman disease was associated with an increased fraction of monocytes which expressed CD56 (N-CAM) (4.1 +/- 2.7% of monocytes, compared to 2.2 +/- 0.5% in ten controls, P < 0.05), an antigen characteristic of immature myeloid cells, suggesting an increased turnover of monocytes. Furthermore, a trend was observed towards an enhanced blood pool of more mature mononuclear phagocytes which show decreased expression of the 55 kD lipopolysaccharide receptor (CD14) together with either expression of the Fc-gamma-receptor III (CD16) or a high expression of CD33. A similar phenotype of peripheral mononuclear phagocytes was observed in the two CESD patients analyzed. In conclusion, our data suggest that these monogenetic defects of lysosomal lipoprotein metabolism are associated with complex alterations of mononuclear phagocyte differentiation and extravasation.
Atherosclerosis 1997 Apr
PMID:Altered mononuclear phagocyte differentiation associated with genetic defects of the lysosomal acid lipase. 912 67

The effect of trifluoperazine (TFP) was investigated on arterial wall lipid-metabolizing enzymes like acyl-CoA:cholesterol acyltransferase (ACAT) and cholesterol ester hydrolase (CEH) in rhesus monkeys. The activity was determined in aortic wall homogenates obtained from rhesus monkeys fed an atherogenic diet coupled with intramuscular injections of adrenaline and TFP. Although TFP had no significant effect on serum cholesterol and triglycerides, it decreased significantly the formation of atherosclerotic lesions by decreasing the esterification of cholesterol, by inhibiting ACAT and enhancing its utilization by activating CEH. Hence, the preventive effect of TFP on the development of atherosclerosis in rhesus monkeys is mediated through its ability to influence the activities of arterial wall lipid-metabolizing enzymes like ACAT and CEH.
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PMID:Effect of trifluoperazine on certain arterial wall lipid-metabolizing enzymes inducing atherosclerosis in rhesus monkeys. 927 Sep 79


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