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 lipid and protein composition of human HDL was changed by incorporation of polyenephosphatidylcholine (PPC) into HDL in vitro. HDL with incorporated PPC (HDL-PPC) had a higher molar PC/apoprotein ratio than native HDL. PPC accounted for up to 50% of the PC fraction of HDL. The fluidity of HDL-PPC was higher than that of native HDL but lower than that of PPC liposomes. Zonal ultracentrifugation separated HDL-PPC into a major and a minor component. The AI/AII ratio of the major fraction was reduced compared with native HDL. The storage capacity of HDL-PPC and native HDL for cholesterol was studied by incubation of these fractions with [14]cholesterol-LDL. Significantly more cholesterol (55%) was taken up by HDL-PPC from LDL than by native HDL. The transfer of cholesterol from LDL to HDL in human serum was studied by an in vitro [14C]cholesterol distribution test. In this test the lipoproteins of serum were labelled with [14C]cholesterol. An analytical procedure was developed to quantify the transfer of cholesterol from LDL to HDL after addition of PC. The transfer depended on the fluidity and the dose of the PC fraction used as well as on the initial LDL + VLDL/HDL ratio and was independent of LCAT activity.
Atherosclerosis 1981 Jul
PMID:Effect of polyenephosphatidylcholine on cholesterol uptake by human high density lipoprotein. 725 31

The phase states and phase transitions of some lipids, lipid mixtures of blood and tissues of some animals and human were examined by the method of scanning calorimetry (DSC-2, "Perkin--Elmer"). It was determined that in monohydrated and in hydrated systems, cholesterol produces a liquefying effect on the total phospholipids of the brain and blood. In complex multicomponent lipid systems changes of the phase states and of temperatures of the phase transitions of some lipids were discovered. The role of these phase transitions and miscibility of lipids for functioning of the cellular membranes and of the key-enzymes in the process of changes of lipoproteins of the blood (LCAT) is being discussed, as well as the connection of the phase transitions of cholesterol esters of the blood with atherosclerosis.
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PMID:[Phase transitions, lipid-lipid interactions and their role in some biostructures]. 732 25

Experimental evidence suggests that aldehydes generated as a consequence of lipid peroxidation may be involved in the pathogenesis of atherosclerosis. It is well documented that aldehydes modify LDL: however, less is known concerning the effects of aldehydes on other plasma and interstitial fluid components. In the present study, we investigated the effects of five physiologically relevant aldehydes (acetaldehyde, acrolein, hexanal, 4-hydroxynonenal [HNE], and malondialdehyde [MDA]) on two key constituents of the antiatherogenic reverse cholesterol transport pathway, lecithin-cholesterol acyltransferase (LCAT) and HDL. Human plasma was incubated for 3 hours at 37 degrees C with each one of the five aldehydes at concentrations ranging from 0.16 to 84 mmol/L. Dose-dependent decreases in LCAT activity were observed. The short-chain (acrolein) and long-chain (HNE) alpha,beta-unsaturated aldehydes were the most effective LCAT inhibitors. Micromolar concentrations of these unsaturated aldehydes resulted in significant reductions in plasma LCAT activity. The short- and longer-chain saturated aldehydes acetaldehyde and hexanal and the dialdehyde MDA were considerably less effective at inhibiting LCAT than were acrolein and HNE. In addition to inhibiting LCAT, aldehydes increased HDL electrophoretic mobility and cross-linked HDL apolipoproteins. Cross-linking of apolipoproteins A-I and A-II required higher aldehyde concentrations than inhibition of LCAT. The alpha,beta-unsaturated aldehydes acrolein and HNE were fourfold to eightfold more effective cross-linkers of apolipoproteins A-I and A-II than the other aldehydes studied. These data suggest that products of lipid peroxidation, especially unsaturated aldehydes, may interfere with normal HDL cholesterol transport by inhibiting LCAT and modifying HDL apolipoproteins.
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PMID:Inhibition of lecithin-cholesterol acyltransferase and modification of HDL apolipoproteins by aldehydes. 758 33

We have studied low density lipoprotein (LDL) subclass distribution in a group of male patients with non-insulin-dependent diabetes mellitus (NIDDM) and investigated its relationships to fasting and postprandial triglyceride (TG)-rich lipoproteins, insulin resistance, lipoprotein lipase (EC 3.1.1.3; LPL), hepatic lipase (EC 3.1.1.34; HL), lecithin:cholesterol acyl transferase (EC 2.3.1.43; LCAT) and cholesteryl ester transfer protein (CETP) activities. LDL was subfractionated by density gradient ultracentrifugation. Postprandial lipoproteins were measured after an oral fat load using retinyl palmitate as a marker for intestinal TG-rich lipoproteins. Hypertriglyceridaemic NIDDMs (HTG) had a preponderance of small dense LDL particles present in the plasma and reduced amounts of large buoyant species when compared to normotriglyceridaemic patients (NTG) and controls. Both groups of diabetics were more insulin resistant than the controls (P < 0.05) and had raised concentrations of proinsulin (P < 0.05), although insulin content did not differ significantly. 32-33 split proinsulin (SPI) was the major insulin-like molecule present in HTG and was present in significantly higher amounts in these patients (P < 0.05) than either NTG or control subjects and correlated significantly with the presence of small dense LDL particles. After a test meal, the postprandial chylomicron response was greater in HTG than either NTG diabetics or controls (P < 0.05). Chylomicron remnants were present to a greater extent in HTG than in NTG and controls (P < 0.05), although in this case NTG also contained more chylomicron remnants than control subjects (P < 0.05). There was no difference in the LPL activity, CETP and LCAT between diabetics and controls, whereas an increase in hepatic lipase activity was seen in the HTG diabetics (P < 0.05). Both CETP and LCAT activities increased postprandially. Multivariate analysis showed that TG, HDL content and HL activity were the most important determinants of small dense LDL concentration in the fasting state (R2 = 67%). Postprandially, chylomicron remnant clearance, HL and insulin resistance were the major determinants (R2 = 61%) of LDL-III.
Atherosclerosis 1995 Mar
PMID:Fasting and postprandial determinants for the occurrence of small dense LDL species in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia: the involvement of insulin, insulin precursor species and insulin resistance. 760 66

High-density lipoproteins (HDL) are believed to protect against atherosclerosis by promoting the process of reverse cholesterol transport. This process involves different steps including efflux of cellular cholesterol, cholesterol esterification and lipid transport and exchange. Apolipoprotein (apo) A-I, the major HDL apolipoprotein, and the HDL-associated enzyme lecithin-cholesterol acyltransferase (LCAT), which uses apo A-I as a cofactor, play a crucial role in reverse cholesterol transport. HDL may be classified into species according to their apolipoprotein content. Recent data concerning HDL particles indicate that lipoproteins containing apo A-I but not apo A-II (LpA-I) are more effective carriers of free cholesterol and are associated with a protective effect against coronary heart disease. In vitro studies have shown that glycosylated HDL are functionally abnormal and may be considered atherogenic. Our study considers the different impacts of non-enzymatic glycosylation of apo A-I or protein-HDL on the reverse cholesterol transport process.
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PMID:Non-enzymatic glycosylation of apolipoprotein A-I and its functional consequences. 762 78

Cigarette smoking is associated with an increased risk of premature atherosclerosis. The underlying mechanisms responsible for this association are unknown. Recent work from this laboratory has shown that ex vivo exposure to plasma to gas-phase cigarette smoke (CS) produces a rapid inhibition of lecithin-cholesterol acyltransferase (LCAT) activity and crosslinking of HDL-apolipoproteins. The goal of the present study was to investigate the mechanism(s) by which CS inhibited LCAT and modified HDL. When dialyzed human plasma (12 ml) was exposed to the gas-phase of an equivalent of 1/8 of a cigarette (one 'puff') at 15 min intervals for 3 h, LCAT activity was reduced by 76 +/- 1% compared to controls; supplementation of plasma with glutathione produced a dose-dependent protection of LCAT activity where at the highest concentration (1 mM) 78% protection was observed. A similar protection was obtained with N-acetyl cysteine (1 mM). In addition to LCAT inhibition, HDL-apolipoproteins were crosslinked after 3 h exposure of plasma to CS; crosslinking was reduced by the addition of either glutathione or N-acetyl cysteine to plasma. The amino compounds N-acetyl lysine, N-acetyl arginine, and aminoguanidine failed to protect LCAT and HDL indicating a specificity with regard to the ability of free thiols to buffer the deleterious components of CS which inhibited LCAT and crosslinked HDL-apolipoproteins. Since LCAT contains two free cysteine residues (Cys-31 and -184) near the active site of the enzyme, we tested whether pretreatment of plasma with the reversible sulfhydryl modifying compound, 5,5'-dithiobis-2-nitrobenzoic acid (DTNB), could protect LCAT from CS-induced inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gas-phase cigarette smoke inhibits plasma lecithin-cholesterol acyltransferase activity by modification of the enzyme's free thiols. 765 78

The possibility that risk of a atherosclerosis complication increases with oral contraceptive use was examined by studying the effect of oral pill containing 0.067 mg menstranol and 0.667 mg ehtynodiol diacetate/kg body weight on the metabolism of lipids in female rats fed a hypercholesterolemic diet for three months. Experimental group clearly exhibited higher levels of triglycerides and cholesterol in plasma and tissues, increase in aorta observed to be two folds. Increased hepatic cholesterogenesis was noted with treatment of oral contraceptive as indicated by higher activity of HMG-CoA reductase. Activity of lipoprotein lipase of extrahepatic tissue was depressed in experimental group. Activity of plasma LCAT, an enzyme involved in the transport of cholesterol from tissues, was also lower with treatment of oral contraceptive. However, activity of malic enzyme and glucose-6-phosphate dehydrogenase enhanced considerably with administration of oral pill. The increase in plasma and aortic cholesterol levels, increase in LDL+VLDL cholesterol and considerable decrease in HDL cholesterol in animals treated with oral contraceptives and fed with atherogenic diet, indicates that prolonged administration of oral pill may predispose towards atherosclerosis.
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PMID:Role of oral contraceptive in atherosclerosis. 792 21

It had been found that Beijing ducks (BD) have a high level of HDL (70%), high LCAT but very low CETP activity and will not develop atherosclerosis on an atherogenic diet, suggesting that cholesterol ester is mainly carried by HDL and metabolized through an HDL receptor pathway in the liver. However, evidence of this receptor's existence in the liver is not yet complete. In this paper, the HDL receptor in BD liver has been studied. Our experiments showed: 1) ApoE-free 125I-HDL could bind specifically to duck hepatic cell membrane with high affinity (Kd = 9.6 micrograms/ml) and was saturable (Bmax = 8.9 micrograms/mg cell membrane protein) at room temperature. 2) Competitive inhibition studies with unlabelled duck, human, rat and chick HDL and duck apo AI and its liposomes formed with PC or DMPC could inhibit the binding of 125I-HDL to duck hepatic cell membranes, but LDL, apo E and their liposomes with PC or DMPC could not with the exception of duck LDL. 3) The receptor could recognize apo AI but not apo B or E. 4) Both phosphorylase A2 and pronase could inhibit the binding activity. The above results give strong evidence for the existence of a specific HDL receptor pathway in the duck liver, supporting our hypothesis that CE in Beijing ducks is metabolized directly through the hepatic HDL receptor instead of being transferred back to VLDL and LDL, then through the LDL receptor pathway. This unique way of metabolizing CE may be behind the Beijing duck's antiatherogenicity.
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PMID:Studies on the HDL receptors. I: Evidence for the existence of HDL receptors in Beijing duck liver. 800 64

We investigated the effects of 12 weeks of bezafibrate treatment on plasma lipoprotein subfraction levels and on activities of LCAT and CETP in 25 patients with hyperlipoproteinemia. Bezafibrate reduced plasma levels of VLDL-TC and VLDL-TG by 69% and 66% (P < 0.001) and plasma levels of IDL-TC and IDL-TG were decreased by 37% and 31% (P < 0.01). Bezafibrate had no significant effects on plasma levels of LDL1 (1.019 < d < 1.045)-TC and LDL1-TG in the study population as a whole but significantly increased the plasma level of LDL1-TC in the subgroup of 9 patients with type IV hyperlipoproteinemia. Bezafibrate reduced plasma levels of LDL2 (1.045 < d < 1.063)-TC, LDL2-TG by 48% and 44% (P < 0.001) in both type II and type IV hyperlipoproteinemic patients. Gradient polyacrylamide gel electrophoresis revealed a decrease in small LDL particles. Bezafibrate did not affect the plasma level of HDL2-TC but reduced the HDL2-TG concentration significantly (P < 0.001). Bezafibrate increased the plasma level of HDL3-TC by 37% and reduced the HDL3-TG level significantly by 20% (P < 0.001). Gradient polyacrylamide gel electrophoresis revealed an increase in HDL3a and a decrease in HDL2a. Bezafibrate suppressed the activities of LCAT and CETP by 21% (P < 0.001) and 17% (P < 0.01), respectively. The bezafibrate-induced decrease in plasma levels of small, heavy LDL might be related to its inhibition of LCAT and CETP activities which resulted in suppression of heteroexchange of HDL-EC with triglyceride in large, light LDL. The bezafibrate-induced increase in large HDL3 (HDL3a) could not be explained solely by its suppression of LCAT and CETP activities. The decrease of plasma small, heavy LDL as well as TG-rich lipoproteins by bezafibrate seems to be beneficial for prevention of atherosclerotic diseases.
Atherosclerosis 1994 Apr
PMID:Effects of bezafibrate therapy on subfractions of plasma low-density lipoprotein and high-density lipoprotein, and on activities of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in patients with hyperlipoproteinemia. 806 Mar 79

To determine the effects of the nephrotic syndrome (NS) on atherogenic risk, we studied the lipoprotein composition and the activities of lecithin-cholesterol acyltransferase (LCAT), lysolecithin acyltransferase (LAT), and cholesteryl ester transfer (CET) in the plasma of 11 NS patients and 10 control subjects. NS plasma had lower ratios of high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and HDL2/HDL3 and an elevated free cholesterol (FC) to phosphatidyl choline (PC) ratio (1.09 +/- 0.27 in NS and 0.72 +/- 0.21 in controls, P < .02), all of which indicate an increased atherogenic potential. LCAT activity was normal in NS plasma when assayed with an exogenous substrate, but was 40% lower than in control plasma when assayed with the endogenous substrates. However, in vitro addition of serum albumin to NS plasma failed to normalize the LCAT activity. The LAT reaction, which is catalyzed by LCAT protein in the presence of LDL, was 60% to 80% higher in NS plasma, and consequently the ratio of LAT/LCAT activities was increased twofold. CET activity was significantly increased (+160% of control), and this abnormality was attributable to changes in both the acceptor (very-low-density lipoprotein [VLDL] + LDL) and donor (HDL) lipoproteins and possibly in CET protein. These results suggest that the NS may increase the risk of atherosclerosis not only by adversely affecting the concentrations of lipoproteins, but also by altering their composition and function.
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PMID:Abnormal acyltransferase activities and accelerated cholesteryl ester transfer in patients with nephrotic syndrome. 808 87


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