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 influence of a dietary supplement of n-3 polyunsaturated fatty acids containing eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) on the molecular species of cholesteryl esters (CE) formed via the plasma lecithin (phosphatidylcholine)-cholesterol acyltransferase (LCAT; EC 2.3.1.43) reaction was evaluated. For this purpose, one group of eight subjects received an encapsulated fish lipid concentrate (MaxEPA) and another group of eight volunteers in the control group received encapsulated olive oil for 22 days. Plasma lipid profiles and fatty acid compositions of plasma phosphatidylcholine (PC) and CE were measured at day 0 and day 22 in all subjects. A decrease in plasma triglyceride (by 34%) and a moderate rise in high-density lipoprotein (HDL)-cholesterol (by 13%) was observed in the MaxEPA group. For characterization of the plasma LCAT-derived reaction products formed in vitro, [14C]cholesterol was used as the substrate and the newly formed molecular species of [14C]CE were separated by argentation thin-layer chromatography. Marked shifts were found in the abundance of the various classes of LCAT-derived products in the MaxEPA group whereas no significant changes were observed in the controls. The proportion of the [14C]CE as pentaenoic (EPA) species rose by 9-fold (from 1.5% at day 0 to 14.4% at day 22) as the dienoic (linoleate) species fell (from 50.6 to 39.2%); a moderate rise in the hexaenoic (DHA) species (from 1.7 to 2.4%) with no significant change in the tetraenoic (arachidonate) (AA) species was observed. The LCAT results were in the order of the observed shifts in the fatty acid patterns of the plasma CE.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1987 Jul
PMID:Alterations in molecular species of cholesterol esters formed via plasma lecithin-cholesterol acyltransferase in human subjects consuming fish oil. 363 42

The effect of chronic oral nicotine intake on plasma low density lipoprotein (LDL) clearance, lipid transfer protein, and lecithin:cholesterol acyltransferase (LCAT) was examined in male atherosclerosis susceptible squirrel monkeys. Eighteen yearling primates were divided into two groups: 1) Controls fed isocaloric liquid diet; and 2) Nicotine monkeys given liquid diet supplemented with nicotine at 6 mg/kg body wt/day for a two-year period. Averaged over 24 months of treatment, animals in the Nicotine group had significantly higher levels of plasma and LDL cholesterol compared to Controls while plasma LCAT activity was similar for both groups. Following simultaneous injection of 3H LDL and 14C high density lipoprotein (HDL) cholesteryl ester (CE), removal of the latter was not altered by oral nicotine while plasma clearance of 3H LDL was dramatically delayed in Nicotine monkeys. Transfer of 14C HDL CE to very low density lipoprotein (VLDL)-LDL particles was greatly accelerated in the Nicotine group vs Controls while the reciprocal movement of 3H LDL CE to HDL was only higher in experimental animals at two time points following injection of the isotopes. Results from this study provide evidence that one major detrimental effect of long-term oral nicotine use is an increase in the circulating pool of atherogenic LDL which is due to: 1) accelerated transfer of lipid from HDL; and 2) impaired clearance of LDL from the plasma compartment. Diminished removal of LDL is of particular importance because an extended residence time of these particles in circulation would increase the likelihood of their deposition in the arterial wall.
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PMID:Oral nicotine impairs clearance of plasma low density lipoproteins. 371 25

The effect of short-term exercise withdrawal on plasma lipoproteins, apoprotein A-I (Apo A-I), and lecithin:cholesterol acyltransferase (LCAT) was studied in moderately trained lifestyle exercisers. Eight endurance-trained men, age 18-45 years (means = 29 years), withdrew from aerobic activity for 6 weeks, while an age and fitness-matched control group (n = 9) maintained normal exercise habits. A baseline period that included two blood samplings preceded the detraining intervention. Plasma total cholesterol (TCHOL), HDL cholesterol (HDL-C) and triglyceride (TG) levels were determined weekly. Other blood variables (HDL2-C, HDL3-C, Apo A-I, and LCAT), % fat, and aerobic capacity (VO2max) were measured pre-, mid-, and post-experiment. A two-way repeated measures analysis of variance (ANOVA) indicated that the 6-week exercise withdrawal period failed to elicit significant mean changes in any blood variable, % fat, or VO2max. Therefore, a short-term layoff from aerobic activity by moderately trained, chronic exercisers generally does not adversely affect the blood lipoprotein profile or aerobic capacity.
Atherosclerosis 1985 Jan
PMID:Response of HDL cholesterol, apoprotein A-I, and LCAT to exercise withdrawal. 392 83

The effect of various chemical and enzymatic modifications of low density lipoprotein (LDL) on its ability to activate the isolated human plasma lysolecithin acyltransferase (LAT) was studied. Removal of all lipids from LDL resulted in the complete loss of LAT activation. Removal of only neutral lipids by extraction with heptane retained up to 50% of the original activity, which was not increased further by reconstitution of the LDL with the extracted lipids. Hydrolysis of the diacylphosphoglycerides of the LDL with phospholipases resulted in complete loss of LAT activation which was partially restored by the addition of egg lecithin. Hydrolysis of more than 4% of LDL protein by trypsin led to a linear decrease in activity with complete loss of activity occurring when about 25% of the LDL protein is hydrolyzed. Modification of the arginine groups of LDL reversibly inhibited the activation of LAT. Modification of lysine residues of LDL by acetylation, acetoacetylation or succinylation also abolished its ability to activate lysolecithin acylation.
Atherosclerosis 1985 Jan
PMID:Role of low density lipoprotein in the activation of plasma lysolecithin acyltransferase activity. Effect of chemical and enzymatic modifications of the lipoprotein on enzyme activity. 392 84

The biochemical, clinical, and genetic features were examined in the proband (homozygote) and heterozygotes (n = 17) affected with familial apolipoprotein A-I and C-III deficiency, variant II (previously described as apolipoprotein A-I absence). The proband was a 45-year-old white female with mild corneal opacification and significant three-vessel coronary artery disease (CAD), who died shortly after bypass surgery. Autopsy findings included significant atherosclerosis in the coronary and pulmonary arteries and the abdominal aorta as well as extracellular stromal lipid deposition in the cornea. No reticuloendothelial lipid deposits in the liver, bone marrow, or spleen were noted (unlike Tangier disease). Laboratory features included marked high density lipoprotein (HDL) deficiency and undetectable plasma apolipoproteins (apo) A-I and C-III. The percentage of plasma cholesterol in the unesterified form was normal at 30%. The activity and mass of lecithin:cholesterol acyltransferase (LCAT) were 42% and 36% of normal, respectively, and the cholesterol esterification rate was 43% of normal. Deficiencies of plasma vitamin E and essential fatty acid (linoleic, C18:2) were also noted. Evaluation of plasma lipoproteins and apolipoproteins in 37 kindred members revealed 17 heterozygotes with HDL cholesterol values below the 10th percentile of normal. Of these, all had apoA-I levels more than one standard deviation below the normal mean, and 37.5% had a similar decrease in apoC-III values. Mean (+/- SD) plasma HDL cholesterol, apoA-I, and apoC-III values (mg/dl) in heterozygotes were 54.0%, 62.4%, and 79.2% of normal, respectively. No evidence of CAD was observed in 10 heterozygotes 40 years of age or less; however, CAD was detected in 3 of 7 heterozygotes over 40 years of age, one of whom died at age 56 years of complications of myocardial infarction and stroke. The inheritance pattern in this kindred was autosomal codominant. ApoA-I isolated from a heterozygote had an isoelectric focusing pattern and amino acid composition similar to normal. Utilizing DNA isolated from two obligate heterozygotes, no abnormalities in the apoA-I or apoC-III genes were detected by Southern blot analysis utilizing specific probes following restriction enzyme digestion. The data indicate that familial apolipoprotein A-I and C-III deficiency, variant II, is similar to variant I (described by Norum et al. 1982. N. Engl. J. Med. 306: 1513-1519), but differs at the clinical level (lack of xanthomas), the biochemical level (lack of detectable apoA-I, lower apoA-II level), and at the gene level.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Familial apolipoprotein A-I and C-III deficiency, variant II. 393 6

We have studied the effect of long-term hyperlipemia and atherosclerosis in squirrel monkeys on the metabolism of lysolecithin-(14)C (1-palmitoyl-1'-(14)C sn-glycerol 3-phosphorylcholine) in order to explain elevated plasma and arterial concentrations of lysolecithin. The die-away curves of lysolecithin-(14)C from plasma and the timing of appearances of other (14)C-labeled moieties in plasma and other tissues demonstrated a complex pattern of metabolic reactions. There was a rapid equilibration of specific activities of lysolecithin of plasma, liver, and aortic intima plus inner media. The specific activities of lecithin peaked first in liver, then in plasma, and rose slowly in aortic intima plus inner media. The appearance of lecithin-(14)C in heart and skeletal muscle was also slower than in the liver and some other tissues. Triglycerides, and to a lesser extent, cholesteryl esters contained radioactivity. The concentrations of aortic lysolecithin in the atherosclerotic aortas were several times greater than comparable values for control aortas, and the time of equilibration of plasma and aorta lysolecithin-(14)C was much greater for the atherosclerotic group. The quantities of lysolecithin in plasma and in the pool of which the plasma was a part, were increased with hyperlipemia and atherosclerosis, as was the rate of lysolecithin production in the fast pool. Hyperlipemia was also associated with an early increase in plasma lecithin:cholesterol acyltransferase (LCAT) activity in vitro. Furthermore, nutritional hyperlipemia influenced the distribution of lysolecithin-(14)C and lecithin-(14)C between different plasma lipoproteins. The increase in concentrations of lysolecithin in the aorta occurred more slowly than that in plasma after we had induced hyperlipemia in the monkeys.
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PMID:Metabolism of lysolecithin in vivo: effects of hyperlipemia and atherosclerosis in squirrel monkeys. 499 21

Epidemiological studies have identified elevated low density lipoprotein (LDL) and diminished high density lipoprotein (HDL) cholesterol levels as risk factors for coronary artery disease. The major protein component of HDL is apoprotein A-I (apo A-I), a polypeptide of 243 amino acids of known primary amino acid sequence. This apoprotein serves as a cofactor for the plasma lecithin-cholesterol acyltransferase (LCAT) enzyme responsible for the formation of most cholesteryl esters in plasma, and also promotes cholesterol efflux from cells. The primary translation product of apo A-I contains both a pre and a pro segment, and post-translational processing of apo A-I may be involved in the formation of the functional plasma apo A-I isoproteins. Defective apo A-I processing may be the underlying problem in Tangier disease, in which patients have low plasma HDL and apo A-I levels despite normal apo A-I synthesis. Patients have been reported with conditions distinct from Tangier disease in whom severe deficiency or absence of apo A-I has been associated with very low HDL levels and severe coronary artery disease. We have now examined the apo A-I gene in two such patients and their first degree relatives. These patients have been reported to have skin and tendon xanthomas, corneal clouding and severe premature coronary atherosclerosis associated with very low HDL levels and deficiencies of two apoproteins, apo A-I and apo C-III. We show that both probands are homozygous for a defect in the apo A-I gene locus.
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PMID:An inherited polymorphism in the human apolipoprotein A-I gene locus related to the development of atherosclerosis. 640 11

Bilateral corneal opacities are the first clinical sign of a familial lecithin-cholesterol acyltransferase (LCAT) deficiency and can be found in early childhood. Familial LCAT deficiency includes the following typical clinical findings: corneal opacification, proteinuria, anemia, turbid or milky plasma, very low plasma HDL, very low plasma cholesterol esters and lysolecithin, hyperlipidemia, and very low or absent LCAT enzymatic activity. Several patients have had fundus findings including angioid streaks and papilledema. This disease is autosomal recessive and has been reported in a total of 19 patients previously. Progression of the disease has resulted in premature atherosclerosis, renal failure and transplantation, decreasing visual acuity and corneal transplantation.
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PMID:Corneal opacification and lecithin-cholesterol acyltransferase (LCAT) deficiency: a case report. 647 90

Incubation of human plasma at 37 degrees C was shown to induce an increase in the electrophoretic mobility of beta-lipoproteins. beta-Lipoproteins were isolated by density gradient ultracentrifugation after such incubation and their composition was analysed. Incubation decreased the content of free cholesterol and increased that of soluble apolipoproteins. The soluble peptides appearing in LDL upon incubation showed 3 major and 2 minor bands upon polyacrylamide disc gel electrophoresis. Two of the major bands corresponded to apolipoprotein C-III-1 and C-III-2 and one of the minor to apolipoprotein C-II. The addition of an inhibitor to lecithin:cholesterol acyltransferase (LCAT) abolished the increase in electrophoretic mobility and to a large extent diminished the other reported effects of incubation. The hypothesis is put forward that during incubation of plasma at 37 degrees C the free cholesterol in the surface of LDL is removed through the action of LCAT, lipid transferases and exchange processes and is replaced in the surface shell by peptides which cause the change in electrophoretic mobility.
Atherosclerosis 1984 Dec
PMID:Increase of electrophoretic mobility and of content of soluble proteins of human plasma beta-lipoproteins by incubation of plasma in vitro. 652 47

Although serum lecithin:cholesterol acyltransferase (LCAT) activity is known to be modulated by nutritional factors, little is known about the effects of dietary carbohydrate on this enzyme. Therefore, LCAT activities were assessed in cynomolgus monkeys fed diets for 6 weeks on 4 diets containing 77% of calories as sucrose or starch and cholesterol at 0 and 1 mg/kcal. Three different assay conditions were used in order to measure the overall LCAT activity and to differentiate enzyme activity from the effect of serum substrate and end-product lipoprotein alterations by diet on this enzyme. Molar rate of serum total LCAT activity was higher in sucrose than starch diets (P less than 0.01). Use of sera from sucrose-fed animals, either as substrate or enzyme source, increased the fractional rate of cholesterol esterification (P less than 0.01). Exogenous cholesterol lowered serum total LCAT activity only in sucrose diet (P less than 0.01). Use of sera from sucrose + cholesterol-fed animals as substrate significantly lowered the fractional rate of cholesterol esterification (P less than 0.01); whereas no such alterations were noted when this serum was used as enzyme source. The differential effect of starch and sucrose diets on LCAT activity suggests that the nature of dietary carbohydrates may affect LCAT activity in association with triglyceride metabolism by altering the amount of enzyme in terms of its activity and/or the nature of substrate and cholesterol ester acceptor lipoproteins.
Atherosclerosis 1983 Apr
PMID:Serum lecithin:cholesterol acyltransferase activities of cynomolgus monkeys fed different carbohydrate diets. 687 Sep 92


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