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)

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

Lipoprotein lipase (lipase), a key enzyme in lipoprotein triglyceride metabolism, has been shown to markedly increase low density lipoprotein (LDL) retention by subendothelial matrix. In the present study we assessed the role that lipoprotein and matrix components play in retention of LDL by lipase anchored to the subendothelial matrix. Lipase addition to subendothelial matrix increased LDL retention by 66-fold. Scatchard analysis of LDL binding to lipase-containing matrix yielded an association constant of 12 nM. Exogenous addition of the matrix components, heparan sulfate and dermatan sulfate (i.e. chondroitin sulfate B), reduced LDL retention by greater than 90%. These glycosaminoglycans (GAGs) also reduced lipolytic activity associated with the matrix, suggesting that lipase was released from its binding sites on the matrix. In contrast, other matrix components (collagen, fibronectin, vitronectin, and chondroitin sulfate A) neither affected LDL release nor matrix lipolytic activity. Thus, heparan sulfate and dermatan sulfate function to anchor lipase to the subendothelial cell matrix. The effects of apolipoprotein E (apoE) and apoA-I were also examined. Preincubation of the subendothelial matrix with apoE, followed by washing, did not affect subsequent lipase binding to the matrix nor its ability to retain LDL. However, the direct addition of apoE alone or in combination with phospholipid liposomes decreased lipase-mediated LDL retention in a concentration-dependent fashion. Addition of apoA-I had no effect. Thus, in these studies apoE functions to displace LDL bound to lipase, but not lipase anchored to the matrix. To further examine the physiologic implications of this process, we assessed the ability of human apoE-rich and apoE-poor high density lipoproteins (HDL) to displace LDL from matrix-anchored lipase. ApoE-rich HDL reduced LDL retention dramatically (86% at 2.5 micrograms/ml). In contrast, apoE-poor HDL, at the highest concentration evaluated (400 micrograms/ml), decreased LDL retention by only 32%. Overall, these data suggest apoE and specifically apoE-containing HDL reduce the lipase-mediated retention of LDL by subendothelial matrix. This observation, in part could explain the protective effects of apoE and apoE-containing HDL against atherosclerosis.
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PMID:Apolipoprotein E modulates low density lipoprotein retention by lipoprotein lipase anchored to the subendothelial matrix. 832 60

A preponderance of small, dense low density lipoprotein (LDL) particles has been linked to increased risk of myocardial infarction, and a dense and protein-rich LDL has proved to be a characteristic of patients with manifest coronary heart disease (CHD). The present study focused on metabolic determinants of the LDL subfraction distribution with the emphasis placed on alimentary lipaemia. The relations of plasma levels and composition of light (1.019 < d < 1.040 kg/l) and dense (1.040 < d < 1.063 kg/l) LDL subfractions to postprandial triglyceride-rich lipoproteins (TGRL), postheparin plasma lipase activities and the activity of cholesteryl ester transfer protein (CETP) were studied in 32 men with angiographically ascertained premature coronary atherosclerosis (age 48.8 +/- 3.2 years) and in 10 age matched healthy control men. LDL subfractions were separated by equilibrium density gradient ultracentrifugation of fasting plasma drawn before participants were subjected to an oral fat tolerance test of a mixed meal type. The response of TGRL to the oral fat load was determined by measuring plasma triglycerides, and the apolipoprotein (apo) B-48 and apo B-100 content of Sf 60-400 and Sf 20-60 lipoprotein fractions. At a second visit plasma samples were taken for determination of postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities and for measurement of CETP activity. Hypertriglyceridaemic patients had a preponderance of dense LDL particles compared with normotriglyceridaemic patients and controls. The magnitude of the response of TGRL to the oral fat load showed a positive association with the dense LDL apo B concentration (r = 0.32-0.52, P < 0.05), whereas the LPL activity correlated positively with the free (r = 0.50, P < 0.001) and esterified cholesterol (r = 0.45, P < 0.01) and apo B (r = 0.42, P < 0.01) content of the light LDL fraction. The HL activity was found to be inversely associated with the plasma level of light LDL triglycerides (r = -0.38, P < 0.05). In contrast, no relations were noted between CETP activity and plasma concentrations of LDL constituents. Multiple stepwise linear regression analysis with the proportion of total LDL apo B contained in the dense LDL subfraction (% dense LDL apo B) used as the dependent variable indicated that the combined effect of LPL activity and postprandial plasma levels of TGRL (areas under the curve for plasma triglycerides or Sf 60-400 apo B-48) accounted for around 50% of the variability in the distribution of LDL particles between light and dense subfractions.(ABSTRACT TRUNCATED AT 400 WORDS)
Atherosclerosis 1993 Jan 04
PMID:Composition of human low density lipoprotein: effects of postprandial triglyceride-rich lipoproteins, lipoprotein lipase, hepatic lipase and cholesteryl ester transfer protein. 845 49

Human aorta was studied at early stages of atherosclerosis: intimal edema, first signs of lipoidosis, lipid spots and lipid plaques. Adhesion of Mn/Mp and lymphocytes to the aortal intima directly correlated with lipid deposits in the vascular wall. The number of mononuclear cells in the intima increased in parallel to progression of lipidosis. T-lymphocyte adhesion passed ahead of that of Mn/Mp. Cytotoxic suppressors dominated among T-lymphocytes adhered to the intima surface. Mn/Mp do not contain enzymes participating in the lipid utilization (acid lipase, acid phosphatase, nonspecific esterase) at initial stages of atherosclerosis. The activity of these enzymes starts to appear in parallel to atherosclerosis progression. HLA-DR antigen is found on the surface of T-lymphocytes and Mn/Mp indicating increased immunity of these cells.
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PMID:[Subpopulations of lymphocytes and monocytes/macrophages at the early stages of human aorta atherosclerosis]. 852 61


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