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)

Thirty postmenopausal women were randomly treated with desogestrel (DG) or levonorgestrel (LN) 125 micrograms/day for 3 weeks. Desogestrel reduced the serum total and free (non-protein bound) testosterone concentrations. It caused a small decrease in the sex hormone binding globulin capacity (SHBG) but did not influence the free testosterone index (testosterone/SHBG ratio). Levonorgestrel, on the other hand, did not influence the free testosterone concentration, but caused a significant increase in the free testosterone index. Levonorgestrel reduced the HDL and particularly the HDL2 cholesterol concentrations (mean change from 1.75 to 1.45 mmol/l for HDL and from 0.73 to 0.50 mmol/l for HDL2, P less than 0.001). It also caused a reduction in the VLDL triglyceride (P less than 0.05) but not the total serum triglyceride concentration. Desogestrel did not cause any significant changes in HDL or HDL2 cholesterol concentrations, but it reduced the VLDL triglyceride (P less than 0.01) and total serum (P less than 0.05) triglyceride concentrations. Neither of the two progestins influenced the postheparin plasma lipoprotein lipase (LPL) activity or the serum cholesterol esterification rate by lecithin:cholesterol acyltransferase (LCAT). It is therefore possible that both steroids decreased the hepatic output of triglycerides, which may be clinically important since both progestins are used in combination with ethinylestradiol (EE) which increases the hepatic TG synthesis. The failure of desogestrel to change HDL levels is consistent with earlier data on the lack of effects on HDL by non-androgenic progestins. Levonorgestrel increased the mean activity of postheparin plasma hepatic lipase (HL) from 23.3 to 28.0 mumol X h-1 X ml-1 (P less than 0.05). In contrast, this activity was not influenced by desogestrel. The magnitude of the changes in postheparin plasma HL activity and the free testosterone index (testosterone/SHBG ratio) showed significant positive correlation (+ 0.41, P less than 0.05). On the other hand, the changes in the HDL2 cholesterol and the postheparin plasma HL activity were inversely interrelated (r = 0.52, P less than 0.01). These relationships are consistent with the idea that the effects of different progestins on the HDL cholesterol are mediated by the sex steroid sensitive hepatic endothelial lipase.
Atherosclerosis 1985 Mar
PMID:Effects of two progestins with different androgenic properties on hepatic endothelial lipase and high density lipoprotein2. 315 21

A number of studies has shown that the plasma levels of high density lipoprotein (HDL) are increased by regular aerobic exercise. The plasma HDL, particularly HDL2, is regulated by the activity of 2 endothelial lipases, viz. lipoprotein lipase (LPL) and hepatic lipase (HL), which both can be assayed in postheparin plasma. In the present study the plasma levels of HDL2 and HDL3 cholesterol and the postheparin plasma lipase activities were related to parameters of physical fitness obtained from a pulse conducted maximal bicycle ergometer test. There was a significant positive correlation between HDL2 cholesterol and physical fitness (r = 0.52, P less than 0.01). On the other hand, the postheparin plasma hepatic lipase activity showed a significant negative correlation to physical fitness (r = -0.57, P less than 0.01). The HDL2 cholesterol was inversely correlated with the HL activity (r = 0.57, P less than 0.001). Application of partial correlation analysis to the data showed that the relationship between HDL2 cholesterol and fitness disappeared by keeping the HL activity constant whereas the correlation between HDL2 and HL was not influenced by fitness. The relation of HDL2 to fitness was independent in body fat and basal plasma insulin level; in addition the relationship between HL and fitness was not accounted for by body fatness. No relationship was found between physical fitness and LPL activity or between HDL3 and fitness. The results support the hypothesis that hepatic endothelial lipase has a role in the regulation of plasma HDL2 cholesterol and that the activity of this enzyme decreases upon increase of physical fitness.
Atherosclerosis 1982 Feb
PMID:Plasma high density lipoproteins HDL2, HDL3 and postheparin plasma lipases in relation to parameters of physical fitness. 706 71

Previous animal studies have shown that the heparin-releasable hepatic lipase (HL) is located on the luminal surface of the liver endothelial cells and may have a function in the removal of high density lipoprotein lipids from plasma. We therefore examined the relationship between plasma HDL levels and the HL activity of postheparin plasma in a group of young, very fit men who were living under strictly controlled comparable conditions (military academy studients). HDL2 cholesterol, HDL2 phospholipid and HDL2 protein concentrations each showed a highly significant negative correlation with postheparin HL activity. A similar but slightly lower inverse relationship was also present between total HDL lipids and HL activity, whereas no correlation could be observed between any of the HDL3 lipids and HL activity. The cholesterol/protein ratio of HDL2 correlated negatively with the HL activity. These results support the hypothesis that the hepatic endothelial lipase has a physiological role in the degradation and removal of circulating HDL2.
Atherosclerosis 1980 Aug
PMID:Evidence for the role of hepatic endothelial lipase in the metabolism of plasma high density lipoprotein2 in man. 741 75

The triglyceride lipase gene family plays a central role in intestinal lipid absorption, energy homeostasis, lipoprotein metabolism, and atherosclerosis. A new member of this gene family, termed endothelial lipase, was recently reported. The presence of key functional motifs, the endothelial synthesis, the enzymatic profile, and the in-vivo metabolic effects of endothelial lipase suggest that, like other members of this gene family, endothelial lipase may play a role in energy delivery to tissues and in modulating lipoprotein metabolism, and could impact on atherogenesis.
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PMID:Endothelial lipase: a new member of the triglyceride lipase gene family. 1078 75

Both lipoproteins and the endothelium play critical roles in the initiation and progression of atherosclerosis. An understanding of the interactions between lipoproteins and the endothelium facilitates our understanding of atherogenesis and could suggest new therapeutic targets. Lipoproteins have important effects on endothelial cells. Atherogenic lipoproteins such as remnants, low-density lipoprotein (LDL), and oxidized LDL act on endothelial cells to cause upregulation of endothelial adhesion molecules and selectins, promotion of oxygen radicals, increased apoptosis, and reduced endothelium-dependent relaxation. Antiatherogenic lipoproteins such as HDL protect endothelial cells from oxidative stress and apoptosis and reduce adhesion molecule expression. Conversely, the endothelium has major effects on lipoprotein metabolism and function. Several lipases, including lipoprotein lipase, hepatic lipase, endothelial lipase, and secretory phospholipase A2, are bound to the endothelial cell matrix and have the ability to hydrolyze lipoprotein triglycerides and phospholipids. Furthermore, endothelial cells express a variety of lipoprotein receptors including the VLDL receptor, scavenger receptor A, SR-BI, CD36, and LOX-1, although little is known about their function on endothelial cells. Although a great deal is known about endothelial-lipoprotein interactions, more research is needed in this important area.
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PMID:The endothelium and lipoproteins: insights from recent cell biology and animal studies. 1112 8

Endothelial lipase (EL) is a newly described member of the triglyceride lipase gene family. It has a considerable molecular homology with lipoprotein lipase (LPL) (44%) and hepatic lipase (HL) (41%). Unlike LPL and HL, this enzyme is synthesized by endothelial cells and functions at the site where it is synthesized. Furthermore, its tissue distribution is different from that of LPL and HL. As a lipase, EL has primarily phospholipase A1 activity. Animals that overexpress EL showed reduced HDL cholesterol levels. Conversely, animals that are deficient in EL showed a marked elevation in HDL cholesterol levels, suggesting that it plays a physiologic role in HDL metabolism. Unlike LPL and HL, EL is located in the vascular endothelial cells and its expression is highly regulated by cytokines and physical forces, suggesting that it may play a role in the development of atherosclerosis. However, there is only a limited amount of information available about this enzyme. Some of our unpublished data in addition to previously published data support the possibility that the enzyme plays a role in the formation of atherosclerotic lesion.
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PMID:Endothelial lipase: a new lipase on the block. 1240 76

High-density lipoprotein (HDL) protects against atherosclerosis. Endothelial lipase (EL) has been postulated to be involved in lipoprotein, and possibly HDL, metabolism, yet the evidence has been scarce and conflicting. We have inactivated EL in mice by gene targeting. EL(-/-) mice have elevated plasma and HDL cholesterol, and increased apolipoproteins A-I and E. NMR analysis reveals an abundance of large HDL particles. There is down-regulation of the transcripts for phospholipid transfer protein, but up-regulation of those for hepatic lipase and lipoprotein lipase. Plasma lecithin:cholesterol acyltransferase is unchanged despite an increase in hepatic mRNA; lecithin:cholesterol acyltransferase activity toward endogenous EL(-/-) substrate is, however, reduced by 50%. HDL clearance is decreased in EL(-/-) mice; both the structure of HDL and the presence of EL are factors that determine the rate of clearance. To determine EL's role in humans, we find a significant association between a single-nucleotide polymorphism 584C/T in the EL (LIPG) gene and HDL cholesterol in a well characterized population of 372 individuals. We conclude that EL is a major determinant of HDL concentration, structure, and metabolism in mice, and a major determinant of HDL concentration in humans.
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PMID:Endothelial lipase is a major genetic determinant for high-density lipoprotein concentration, structure, and metabolism. 1260 Nov 78

The endothelium interacts extensively with lipids and lipoproteins, but there are very few data regarding the ability of endothelial cells to secrete lipases. In this study, we investigated the ability of endothelial cells to secrete the triglyceride lipase and phospholipase activities characteristic of endothelial lipase (EL), a recently described member of the triglyceride lipase gene family. No lipase activities were detected under basal conditions, but treatment with cytokines significantly stimulated the expression of both activities. Using antibodies to EL, we determined that both activities were primarily a result of this enzyme. In addition to the increase in lipolytic activity, cytokine treatment was demonstrated to substantially upregulate EL protein and EL mRNA in a dose-dependent manner. Cytokines did not change EL mRNA stability. Both new protein synthesis and activation of NF-kappaB influenced the induction of EL by cytokines, suggesting that multiple pathways contribute to this process. The upregulation of EL by cytokines is in sharp contrast to the downregulation by cytokines of the other two major members of this gene family, lipoprotein lipase and hepatic lipase, and has implications for the physiological role of EL in inflammatory conditions and its potential role in the modulation of lipoprotein metabolism during inflammatory conditions, including atherosclerosis.
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PMID:Endothelial cells secrete triglyceride lipase and phospholipase activities in response to cytokines as a result of endothelial lipase. 1260 72

Endothelial lipase (EL), a new member of the lipase gene family, was recently cloned and has a significant role in plasma high-density lipoprotein levels (HDL). EL has a highly similar molecular homology to lipoprotein lipase and hepatic lipase. It is synthesized by endothelial cells and functions at the cell surface. EL primarily has phospholipase A1 activity. Animals that overexpress EL showed decreased HDL cholesterol levels and those that lack EL show elevated levels of HDL cholesterol. The expression is highly regulated by cytokines and physical forces. These data suggest that EL may play a significant role in atherosclerosis.
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PMID:Endothelial lipase and cholesterol metabolism. 1502 97

We are continuing to both elucidate underlying mechanisms and identify clinical applications for a chemically induced murine model of dose-controlled hyperlipidemia and atherosclerosis. This murine model neither utilizes genetically modified mice nor a high-fat, cholate-containing diet, although simultaneous ingestion of a high-fat, cholate-enriched diet potentiates the hyperlipidemic response and the number and size of aortic atherosclerotic lesions formed in C57BL/6 mice. The chemical agent used to induce hyperlipidemia is poloxamer 407 (P-407), a nonionic surface-active-agent. To date, we have investigated the effect of P-407 on the biologic activity of a variety of key enzymes involved with lipid metabolism and transport. These enzymes include 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, lipoprotein lipase (LPL), cholesterol 7alpha-hydoxylase (C7alphaH), sterol 27-hydroxylase (S27H), lecithin cholesterol acyltransferase (LCAT), cholesteryl-ester-transfer-protein (CETP), hepatic lipase (HL), and endothelial lipase (EL). P-407 directly inhibits the heparin-releasable fraction of LPL and HL and indirectly increases the biologic activity of CETP and LCAT. Long-term (> 4 months) administration of P-407 to C57BL/6 mice appears to have no effect on the biologic activity of S27H and HMG-CoA reductase, but decreases the activity of C7alphaH. This would suggest that hypertriglyceridemia and hypercholesterolemia result from inhibition of LPL and C7alphaH, respectively, while the biologic activity of CETP and LCAT are indirectly increased to compensate for the increased cholesterol burden. The above model has proven useful for predicting the therapeutic efficacy of existing and possibly newer statin drugs, as well as evaluating the potential of one statin drug (atorvastatin calcium) to cause the regression of P-407-induced atherosclerotic lesions in mice. The P-407-induced murine model of atherogenesis represents an alternative to the use of either genetically modified or diet-induced models and may also prove beneficial for the evaluation of newer classes of antihyperlipidemic agents such as antioxidants, CETP inhibitors, and liver X receptor (LXR) agonists.
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PMID:The P-407-induced murine model of dose-controlled hyperlipidemia and atherosclerosis: a review of findings to date. 1508 72


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