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)

We have examined the effect of added apolipoprotein A-I (apoA-I) on the changes in high density lipoprotein (HDL) particle size that occur when human plasma is incubated in vitro. In the absence of added apoA-I, incubation of plasma at 37 degrees C resulted in a dramatic increase in HDL particle size. When these incubations contained an inhibitor of LCAT, an additional population of smaller HDL particles was formed. These changes in particle size were even more pronounced when the incubations were supplemented with an artificial triglyceride emulsion, Intralipid. All these changes in HDL particle size were markedly inhibited when incubations were supplemented with apoA-I. Even when the amount of added apoA-I was as little as 4.5% of the endogenous apolipoprotein there was an obvious inhibition of the changes in HDL particle size. The presence of added apoA-I sufficient to increase the plasma concentration by 18% virtually abolished the changes in HDL particle size. This effect did not relate to an inhibition of cholesterol esterification, nor did it appear to depend on an incorporation of the added apoA-I into the HDL.
Atherosclerosis 1989 Jan
PMID:Apolipoprotein A-I inhibits transformation of high density lipoprotein subpopulations during incubation of human plasma. 293 Jun 15

The plasma lipoproteins are the primary means of transport of cholesterol among tissues. In particular, the apo B-containing lipoproteins (VLDL, IDL and LDL) are important for the delivery of cholesterol from the liver to peripheral tissues, while HDL appear to mediate the reverse process of movement of cholesterol from tissues back to the liver. Both of these transport processes are necessary for efficient whole body cholesterol homeostasis, because the liver is the major site of both the production and excretion of cholesterol. However, deviations from a proper balance of transport of cholesterol, either increases in LDL levels or decreases in HDL cholesterol flux, may result in accumulation of cholesterol in extrahepatic tissues. Increased risk of atherosclerosis and CHD may be associated with elevation in the number of LDL particles, increase or decrease in LDL particle size, or changes in the composition of plasma LDL. These modifications of plasma LDL may be brought about following perturbation of one of several aspects of LDL metabolism. These include decreased LDL receptor activity, increased VLDL production and cholesterol enrichment of the liver-derived VLDL. The events in the arterial wall that make some LDL particles apparently atherogenic are not well understood. In the case of nonhuman primates, large-size LDL are associated with an increased risk of CHD. One characteristic of these LDL is that their core lipids are rich in saturated cholesteryl esters and their transition temperatures are frequently above body temperature. The liquid crystalline cholesteryl ester cores of such LDL may modulate the conformation of apo B on the surface and thereby affect the interaction of these LDL with cellular receptors or connective tissue matrix proteoglycans. It is likely, though, that changes in LDL particle number, LDL particle size and LDL particle composition may each contribute to progression of atherosclerosis. The presumed metabolic events that make HDL protective against atherosclerosis have been termed reverse cholesterol transport, and suggest that small HDL that are deficient in free cholesterol acquire this lipid from cell membranes. The HDL cholesterol is esterified by LCAT in the circulation, forming large HDL that can then deliver the cholesteryl ester to the liver by both direct and indirect means. In most circumstances, it is assumed that an increase in plasma HDL cholesterol concentration reflects an increase in the rate at which HDL is removing cholesterol from tissues and, consequently, a decrease in atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lipoproteins and atherosclerosis. 333 Apr 21

The transfer of insoluble cholesteryl esters among lipoprotein particles is a vital step in normal cholesterol homeostasis and may be involved in the development of atherosclerosis. Extrahepatic tissues lack the enzymes required for the degradation of sterols to the excretable form of bile acids. Cholesterol synthesized in these tissues in excess of that needed for the synthesis of cell membranes or steroid hormones must accordingly be returned through the plasma to the liver for catabolism. The series of reactions involved has been termed reverse cholesterol transport. Catalysed steps of this pathway are believed to include an efflux from peripheral cells, which generates a diffusion gradient between these membranes and extracellular fluid; esterification of this cholesterol by lecithin-cholesterol acyltransferase (LCAT) (phosphatidylcholine-sterol acyltransferase) acting on species of high-density lipoproteins; transfer of the cholesteryl esters formed (largely to low- and very low-density lipoproteins) (LDL and VLDL) by a cholesteryl ester transfer protein (CETP); and removal of these lipoproteins, together with their cholesteryl ester content, by the liver through receptor-mediated and nonspecific endocytosis. Of these steps, the CETP reaction is the least characterized. Several laboratories have reported the purification from human plasma of proteins active on cholesteryl ester transfer between lipoprotein particles and possibly between cells and plasma. However, the reported relative molecular mass (Mr), abundance and specificity of the purified activities have differed considerably. We have recently described the preparation of a highly active CETP of Mr 74,000 purified about 100,000-fold from human plasma, which may represent the functional component of earlier preparations. Using a partial amino-acid sequence from this purified protein, CETP complementary DNA derived from human liver DNA has been cloned and sequenced and the cloned DNA used to detect CETP messenger RNA in a number of human tissues.
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PMID:Cloning and sequencing of human cholesteryl ester transfer protein cDNA. 360 Jul 59

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

Lipoprotein patterns and cholesteryl ester transfer activity (CETA) were examined in 2 patients with familial hyperalphalipoproteinaemia (FHALP). The proband was a healthy 58-year-old Japanese male who had an HDL cholesterol of 7.83 mmol/l (301 mg/dl). His sister's HDL cholesterol was 4.52 mmol/l (174 mg/dl), which suggested that both were homozygous carriers of FHALP. In both subjects HDL showed a high cholesterol/apo A-I ratio and appeared to be a larger-sized particle than normal HDL on agarose gel chromatography. Two of the proband's children showed higher HDL cholesterol levels (1.74 mmol/l, 2.16 mmol/l) than normal, but another 2 children showed normal levels (1.48 mmol/l, 1.40 mmol/l). However, the ratios of HDL cholesterol to total cholesterol and to apo A-I in all children were higher than normal. These data suggest, but do not prove, that all his children were heterozygotes. Apo B levels in all of the family members studied were lower than normal (47-80 mg/dl). Deceased members of the same family had not died from cardiovascular disease. Cholesteryl-ester transfer activity was studied in both patients. When serum or lipoprotein deficient serum (d greater than 1.21) and [3H]cholesteryl ester labelled HDL3 were incubated in the presence of an LCAT inhibitor, there was no evidence of cholesteryl ester transfer from HDL to VLDL and/or LDL, unlike normal subjects. The deficiency of CETA in these patients with FHALP presumably accounted for the increase in particle size and cholesterol enrichment of HDL.
Atherosclerosis 1985 Dec
PMID:Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia. 393 35

Concentrations of HDL cholesterol, apolipoprotein (apo) A-I and apo A-II were found to be significantly decreased in patients with insulin-dependent diabetes (IDD) and non-insulin-dependent diabetes (NIDD) compared with carefully selected controls matched for sex, age and body weight. LDL cholesterol and apo B levels did not differ significantly between diabetics and controls. Concentrations of lipoprotein Lp(a), an independent risk factor for coronary artery disease in non-diabetics, were above 20 mg/dl in only 14% of diabetics and in 5% of controls. LCAT activity was normal in diabetics, irrespective of type of diabetes, sex and age of patients. No correlation between HbA1 and either HDL cholesterol or A-I and A-II was found in IDD and NIDD. A positive correlation between HbA1 and either triglyceride or VLDL triglyceride was noted in IDD and NIDD. There was also a positive correlation between insulin dosage in IDD and HDL cholesterol, apolipoprotein A-I and A-II.
Atherosclerosis 1983 Dec
PMID:Apolipoproteins (A-I, A-II, B), Lp(a) lipoprotein and lecithin: cholesterol acyltransferase activity in diabetes mellitus. 622 55

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

An esterifying activity of blood plasma (lecithin-cholesterol-acyl transferase, LCAT) was decreased in men with ischemic heart disease (IHD) and coronary atherosclerosis as compared with patients without any symptoms of IHD; the decrease of the activity was most distinct in patients with low level of cholesterol in high density lipoproteins (HDL) and with hyperlipidemia. In these patients phospholipid composition of HDL subfractions was altered: a decrease in the lecithin ratio, increase in the content of sphingomyelin and corresponding decrease in the ratio lecithin/sphingomyelin. Decrease in content of HDL cholesterol and in concentration of apo A-I in blood, plasma, alterations in phospholipid composition of HDL subfractions and in the rate of fatty acids unsaturation of HDL phospholipids in the patients with IHD were considered as factors responsible for the decrease of LCAT activity, which may aggravate the atherosclerotic impairment of arteries.
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PMID:[Esterifying activity of the plasma in patients with ischemic heart disease]. 652 15

Benzodiazepine drugs have been reported to have antiatherosclerotic effects in rabbits and roosters and to alter the pattern of circulating lipoproteins in man. The mechanism(s) of these effects has not been elucidated. The studies presented here indicate that diazepam, the most widely used benzodiazepine, is an inhibitor of cholesterol esterification by ACAT in vitro in atheromatous rabbit aortas, in microsomes isolated from atheromatous rabbit aortas, and in normal rat aortas. Diazepam also inhibited LCAT in plasma from man, monkey, rabbit, and rat, in vitro. The ability of diazepam to inhibit these enzyme systems may offer insight into possible in vivo mechanisms of action against atherosclerosis and of lipoprotein modification.
Atherosclerosis 1984 Mar
PMID:Diazepam inhibits cholesterol esterification by arterial ACAT and plasma LCAT, in vitro. 671 79


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