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 mechanism whereby alcohol increases high-density lipoprotein cholesterol (HDL-C) levels is unclear. Lipoprotein lipase (LPL), hepatic lipase (HL), cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT) act on lipoprotein metabolism. The purpose of the present study is to determine which one or what combination of these factors is responsible for the rise in HDL-C levels following alcohol ingestion. After 3 weeks of abstinence, 12 men consumed 0.5 g/kg bw of alcohol per day for 4 weeks; 13 abstaining men served as controls. Mean plasma total cholesterol (TC) levels were unchanged in either group throughout the study. Among the alcohol consumers, plasma triglycerides (TG), HDL-C, apolipoprotein (apo) A-I and A-II levels increased significantly after 3 weeks of alcohol loading but were unchanged in the control group. High-density lipoprotein3 cholesterol (HDL3-C) levels increased significantly in the alcohol consumers after 4 weeks of alcohol loading whereas high-density lipoprotein2 cholesterol (HDL2-C) levels were unaffected. In the controls, neither HDL2-C nor HDL3-C changed significantly. Post-heparin plasma (PHP) LPL activity and mass increased significantly (P < 0.01) after the alcohol ingestion (controls remained unchanged) without changing LPL specific activity. HL, CETP and LCAT activities were unaffected in both groups. We conclude that of the factors considered, LPL contributed the most to the alcohol-induced rise in HDL-C.
Atherosclerosis 1994 Nov
PMID:Effects of alcohol on lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein, and lecithin:cholesterol acyltransferase in high-density lipoprotein cholesterol elevation. 784 Aug 18

Human hepatic triglyceride lipase (HTGL) is a 476 residue glycoprotein that hydrolyzes triglyceride rich lipoproteins and high density lipoproteins. Comparison of the HTGL, LPL and PL gene structures established them as members of a lipase gene family. Familial HTGL deficiency is a rare disorder that is characterized by premature atherosclerosis and abnormal circulating lipoproteins. In HTGL transgenic mice, plasma HDL cholesterol and total cholesterol levels were found to be low and were correlated with decrease in the accumulation of aortic cholesterol. These results suggest that HTGL may have a protective effect against formation of atherosclerosis.
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PMID:[Hepatic triglyceride lipase]. 785 4

Clofibrate has cholesterol- and triglyceride-lowering effect. They affect on the various points in the metabolic pathway of lipoproteins. They improve VLDL-synthesis in liver and increase the activity of LPL and hepatic TG lipase. As the results, HDL-cholesterol increases and LDL decreases. Therefore Clofibrate decreases not only plasma triglyceride but cholesterol levels. It has been reported that Clofibrate have a preventive effect on cardiovascular disease. So these agents are useful in the treatment for hyperlipidemic patients with or without atherosclerosis.
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PMID:[Clofibrate treatment of hyperlipoproteinemia]. 785 24

The influence of hepatic lipase (HL) and lipoprotein lipase (LPL) activity on the low density lipoprotein (LDL) subclass pattern was studied in a population of males with coronary heart disease and without severe hypercholesterolemia. LDL subclass patterns, lipases and plasma lipoproteins were determined in 326 patients. In part of the study population, fasting insulin and glucose levels were also determined. The LDL subclass pattern was determined by gradient gel electrophoresis (GGE) and classified according to Austin et al. (J. Am. Med. Assoc. 260 (1988) 1917 (predominantly large LDL = A-pattern, predominantly small LDL = B-pattern). An LDL subclass A-pattern was exhibited by 199 subjects; 108 exhibited a B-pattern. In 19 subjects no distinctive A- or B-pattern was present (A/B-pattern). Hepatic and lipoprotein activities differed significantly between patients with the A- or B-pattern. The median hepatic lipase activity was lower (384 vs. 417 mU/ml, P = 0.006), and the lipoprotein lipase activity higher (122 vs. 101 mU/ml, P = 0.001) in the A-pattern subjects than in the B-pattern subjects. In subjects with the A/B pattern the lipase activities were intermediate between the values in the A- and B-pattern subjects (HL 408 +/- 87 mU/ml, LPL 115 +/- 55 mU/ml). Plasma triglyceride, very low density lipoprotein (VLDL)-triglyceride, intermediate density lipoprotein (IDL)-triglyceride and LDL-triglyceride were higher in the patients with a B-pattern (+84%, +171%, +10% and +16%, respectively). Total plasma cholesterol was not different between A- and B-pattern subjects. VLDL- and IDL-cholesterol were higher in the B-pattern group (+174% and +66%, respectively), while LDL- and HDL-cholesterol were higher in the A-pattern group (+2 and +24%, respectively). In univariate analysis HL, LPL, plasma (and VLDL) triglyceride, HDL-cholesterol and IDL-cholesterol were each significantly associated with the LDL subclass pattern. In multivariate analysis plasma triglyceride (or VLDL-triglyceride) and HDL-cholesterol appeared to be independently associated with the LDL subclass pattern. No additional discriminative value of HL or LPL was found. Similar results were obtained if the patients with or without beta blocker were evaluated separately. An estimate of insulin resistance (EIR), calculated from plasma insulin and glucose in part of the study population (n = 145), was significantly higher in the subjects with a B-pattern than in those with an A-pattern (3.12 vs. 2.00, P < 0.003). EIR correlated positively with plasma triglyceride (P < 0.0001), but not with HL or LPL.(ABSTRACT TRUNCATED AT 400 WORDS)
Atherosclerosis 1994 May
PMID:Hepatic lipase and lipoprotein lipase are not major determinants of the low density lipoprotein subclass pattern in human subjects with coronary heart disease. 794 58

It has previously been shown that lipoprotein lipase can mediate uptake of remnant lipoprotein particles via binding to the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP). Binding of lipoprotein lipase, and of triglyceride-rich lipoproteins associated with the lipase, to LRP depends on an intact carboxyl-terminal folding domain of the lipase (Nykjaer, A., Bengtsson-Olivecrona, G., Lookene, A., Moestrup, S. K., Petersen, C. M., Weber, W., Beisiegel, W., and Gliemann, J. (1993) J. Biol. Chem. 268, 15048-15055). Here we show that the site for binding to the receptor is within residues 380-425 of the bovine and residues 378-423 of the human lipoprotein lipase. We demonstrate that a carboxyl-terminal fragment of human lipoprotein lipase (residues 378-448), expressed as fusion protein in Escherichia coli, binds to purified and cellular LRP but not to lipoproteins. Binding of the fragment to purified LRP was blocked by heparin. In addition, the fragment inhibited the binding of lipase and the lipase-mediated binding of lipoproteins to the purified receptor. The fragment exhibited reduced binding to proteoglycan-deficient cells. Moreover, the fragment inhibited the uptake of lipoproteins in cells mediated by the lipase via binding to heparan sulfate proteoglycans and LRP. We conclude that the fragment contains the site for binding to LRP and a candidate site for interaction with heparan sulfate proteoglycans, whereas binding to lipoproteins is inefficient. The fragment can therefore inhibit the lipase-mediated lipoprotein uptake, a process that may promote the development of atherosclerosis when occurring in cells of the arterial wall.
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PMID:A carboxyl-terminal fragment of lipoprotein lipase binds to the low density lipoprotein receptor-related protein and inhibits lipase-mediated uptake of lipoprotein in cells. 798 48

Several lipases and their cofactors are involved in the absorption, transport, storage, and mobilization of lipids. As part of an effort to examine the role of these enzymes in plasma lipid metabolism and genetic susceptibility to atherosclerosis, we report the chromosomal mapping of their genes in mouse. Restriction fragment length variants for each gene were identified, typed in an interspecific cross, and tested for linkage to known chromosomal markers. The gene for pancreatic lipase resides on chromosome 19, while the gene for its cofactor, colipase, is on chromosome 17. A gene for a protein with sequence similarity to pancreatic lipase was tightly linked (no observed recombination) to the gene for pancreatic lipase, suggesting a gene cluster. The gene for hormone-sensitive lipase is near the gene cluster containing apolipoproteins C-II and E on chromosome 7. The gene for hepatic lipase is near the gene for apolipoprotein A-I on chromosome 9. The carboxyl ester lipase gene resides on chromosome 2. Previously, we have mapped the gene for lipoprotein lipase to chromosome 8. Thus, with the exception of pancreatic lipase and a related protein, these lipase genes, including several that are members of a gene family, are widely dispersed in the genome. Comparison of chromosomal locations for these genes in mouse and humans shows that the previously observed interspecies syntenies are preserved.
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PMID:Chromosomal localization of lipolytic enzymes in the mouse: pancreatic lipase, colipase, hormone-sensitive lipase, hepatic lipase, and carboxyl ester lipase. 810 16

Individuals with hepatic lipase (HL) deficiency are often characterized by elevated levels of triglycerides and cholesterol and may be subject to premature atherosclerosis. Missense mutations in the HL gene have been identified in two affected families: substitutions of serine for phenylalanine at amino acid 267 and threonine for methionine at amino acid 383 (S267F and T383M, respectively). To confirm the role of S267F and T383M, respectively). To confirm the role of mutations separately into human HL cDNA by site-directed mutagenesis, and the resulting constructs were independently expressed in COS cells. HL activity and mass were measured and compared with wild-type HL transfectants to determine the effect of these mutations on lipase activity and secretion. Although similar amounts of HL protein were detected intracellularly after transfection with the wild-type and mutant constructs, S267F and T383M HL activity levels were markedly decreased: in S267F, no HL activity was detected, and activity levels in T383M were 38% of wild-type HL. Heparin-induced secretion of the two HL mutants was also severely affected: no detectable activity could be measured in the media of S267F, although some inactive mass (12% of wild-type HL) was secreted; mutant T383M secreted 4% and 20% of wild-type activity and mass, respectively. These results indicate that the single amino acid substitution present in HL S267F is sufficient to render the enzyme completely nonfunctional; in contrast, the T383M mutant retains partial activity but is poorly secreted. Thus, these defects appear capable of accounting for the HL-deficient phenotypes exhibited by individuals carrying the T383M and S267F mutations.
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PMID:Molecular characterization of human hepatic lipase deficiency. In vitro expression of two naturally occurring mutations. 812 42

Acid lipase activity (ALA) and neutral lipase activity (NLA) in lymphocytes of patients with primary hyperlipidemia (hypercholesterolemia or/and hypertriglyceridemia) were compared with that of an age-matched control group (blood donors). The specificity of lipase was confirmed by the use of cardiolipin the well known activator of acidic lipase. beta-D-glucuronidase activity was used as a marker of the lysosomal release reaction. ALA (by 33%) and beta-D-glucuronidase (by 55%) activity, but not NLA in lymphocytes of the group of hyperlipidemic patients, was significantly lower when compared to the control group. A negative correlation between the serum cholesterol level and ALA, NLA and beta-D-glucuronidase release from lymphocytes of hyperlipidemic subjects was observed. The serum HDL cholesterol level was positively correlated with ALA within this group. These results suggest that the high cholesterol level in serum can unspecifically supress ALA and (to the smaller degree) NLA activity in lymphocytes of hyperlipidemic subjects. The decrease of lipase activity may promote deposition of lipids in cells and the development of atherosclerosis. The parallel decrease of beta-D-glucuronidase activity in lymphocytes of hypercholesterolemic patients suggests the impairment of immune system in hypercholesterolemia.
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PMID:Acid and neutral lipase activity in lymphocytes of patients with increased serum cholesterol and triglyceride level. 812 83

Working muscle plays a central role in the control of lipid metabolism. Increased physical activity induces a number of positive changes in the metabolism of lipoproteins: serum triglycerides are lowered by the increased lipolytic activity and the production of native high density lipoprotein (HDL) particles is increased. The increased lecithin: cholesterol acyltransferase activity leads to an increased production of HDL2, which in addition is catabolised more slowly due to a decreased activity of hepatic lipase. The 3 effects explain the increased HDL levels of endurance trained individuals. These effects have been demonstrated in cross-sectional as well as longitudinal studies by different groups, and can be induced by training, independent of changes in bodyweight. The influence of endurance activity on the quality and quantity of low density lipoprotein (LDL) particles is a further reason for the antiatherogenic potential of increased physical activity. It has been shown by several groups that small dense LDL particles represent a particular risk factor for atherosclerosis. Recent studies presented strong evidence that LDL level and composition can be influenced favorably by physical activity. In addition to the direct influence of physical activity on lipids and lipoproteins, physical exercise may improve the disturbances of haemorheological factors, particularly those associated with hypertriglyceridaemia. In conclusion, there is increased evidence that physical activity is able to favourably influence all 3 components of the atherogenic lipoprotein phenotype: the HDL concentration increases, the concentration of small dense LDL decreases, and serum triglycerides are reduced.
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PMID:Physical activity and lipoprotein lipid disorders. 815

Twenty patients (18 men, 2 women) with non-insulin dependent diabetes mellitus (NIDDM) were randomized to receive either gemfibrozil 1200 mg daily or placebo for 3 months in a double-blind study. The effect of gemfibrozil on plasma HDL subfraction distribution was studied with sequential and density gradient ultracentrifugation and in gradient gel electrophoresis. The concentrations of apo A-I, apo A-II, Lp A-I and Lp A-I:A-II particles were measured. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities and plasma cholesteryl ester transfer protein (CETP) activities were also determined. Gemfibrozil increased the concentration of HDL cholesterol (P < 0.01), which was due to the rise of HDL3 cholesterol (+16%), while in the placebo group these values remained unchanged. Gemfibrozil increased the concentrations of apo A-I(+12.6%, NS), apo A-II (+28.2%, P < 0.01) and Lp A-I:A-II particles (+21.6%, P < 0.06) but there were no changes in the placebo group. Neither gemfibrozil nor placebo had any effect on the concentration of Lp A-I particles. As determined by density-gradient ultracentrifugation, gemfibrozil increased the concentration of cholesterol in the most dense HDL fractions (mean density 1.193 g/ml, +22%, P < 0.05 and mean density 1.158 g/ml, +19.3%, P < 0.05). In gradient gel electrophoresis, the gemfibrozil-induced elevations of the cholesterol and protein were most pronounced in the HDL3a (8.8-8.2 nm) region. Gemfibrozil increased LPL and HL activities by 14.7% (P < 0.05) and by 18.8% (P < 0.01), respectively, while in the placebo group LPL and HL activities remained unchanged. Plasma CETP activity was also increased during gemfibrozil treatment while in the placebo group it remained unchanged. We conclude that gemfibrozil causes multiple changes in plasma HDL metabolism. The gemfibrozil-induced elevation of HDL3 and dense HDL subpopulations may reflect the concerted action of LPL, HL and CETP on plasma HDL metabolism.
Atherosclerosis 1993 Aug
PMID:Effect of gemfibrozil on high density lipoprotein subspecies in non-insulin dependent diabetes mellitus. Relations to lipolytic enzymes and to the cholesteryl ester transfer protein activity. 825 55


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