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 recently reported that the human apolipoprotein A-I (apoA-I) and apolipoprotein C-III (apoC-III) genes are physically linked and that the presence of a DNA insertion in the apoA-I gene is correlated with apoA-I-apoC-III deficiency in patients with premature atherosclerosis. In addition, the presence of a polymorphic restriction endonuclease site (SacI) in the 3' noncoding region of apoC-III mRNA has been correlated with hypertriglyceridemia in humans. In this study, we report the isolation and characterization of cDNA clones containing the entire apoC-III mRNA coding sequence. The nucleotide-derived apoC-III amino acid sequence indicates that the apoC-III primary translational product contains a 20 amino acid N-terminal extension, which conforms with the general properties of known signal peptides, and is highly homologous to the recently reported rat apoC-III signal peptide. The DNA-derived apoC-III amino acid sequence differs from the previously reported apoC-III amino acid sequence at four amino acid residues. More specifically, at positions +32, +33, +37, +39, the DNA sequence predicts Glu, Ser, Gln, Ala, respectively, while the previously reported sequence specifies Ser, Gln, Ala, Gln, respectively. Finally, isolation and characterization of apoC-III cDNA clones, with or without the polymorphic SacI restriction site, indicated that the apoC-III nucleotide sequence corresponding to the Sac+ and Sac- clones differs at three nucleotide sites; however, the amino acid sequence specified by the Sac+ and Sac- alleles is identical.
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PMID:Isolation and characterization of cDNA clones corresponding to two different human apoC-III alleles. 298

We have studied the effect of lovastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase), alone and in combination with the bile acid sequestrant cholestyramine on lipid parameters in 30 heterozygous patients with familial hypercholesterolemia (FH) during a 20-week open trial. Lovastatin 40 mg bid (twice daily) decreased significantly total serum cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides and apolipoprotein B by 36%, 45%, 29% and 11%, respectively, while high density lipoprotein (HDL)-cholesterol and apolipoprotein A-I were increased significantly by 16% and 37%, respectively. These data are consistent with a reduction in both the number of LDL particles and in their cholesterol content. Addition of cholestyramine 4 g bid caused a significant further decrease in total serum cholesterol and LDL-cholesterol to a total of 43% and 61%, respectively. The addition of 4 g bid or 8 g bid of cholestyramine caused only minor changes in the other lipid parameters. No effect was found by these drugs on Lp(a) lipoprotein level. We conclude that lovastatin alone or in combination with a small dose of cholestyramine normalizes the lipid profile in most FH heterozygotes.
Atherosclerosis 1988 Oct
PMID:Effects of lovastatin alone and in combination with cholestyramine on serum lipids and apolipoproteins in heterozygotes for familial hypercholesterolemia. 305 29

The addition of cholesterol-poor phospholipid liposomes to canine plasma in vivo and in vitro substantially alters the distribution of phospholipids, apoproteins, and, especially, cholesterol. In vivo, intravenously injected phospholipid liposomes remain discrete particles, which are readily distinguished from the normally occurring lipoproteins by their buoyant density and electrophoretic mobility. They acquire unesterified cholesterol from endogenous sources, thereby producing an acute rise in the concentration of this sterol in plasma. The liposomes also accumulate endogenous proteins, one of which is identified as apolipoprotein A-I. In vitro, phospholipid liposomes incubated with plasma acquire unesterified cholesterol and apolipoprotein A-I at the expense of high-density lipoproteins (HDL), the major carrier of cholesterol in normal canine plasma. In exchange, the HDL particles are enriched in phospholipids and become larger. At sufficiently high concentrations, the liposomes nearly completely deplete HDL of its unesterified cholesterol. Thus, there are generated two types of particles, both rich in apolipoprotein A-I and phospholipid, but one (modified HDL) containing mainly esterified cholesterol in its core and the other (modified liposomes) containing mainly unesterified cholesterol at its surface. It is concluded that phospholipid liposomes produce important changes in the distribution of lipids and protein in canine plasma, particularly at the expense of HDL. These changes appear to favor the mobilization of tissue cholesterol into the plasma, and may have application to atherosclerosis.
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PMID:Uptake of endogenous cholesterol by a synthetic lipoprotein. 308 25

High density lipoprotein (HDL) cholesterol, apolipoprotein A-I (apo A-I), gamma-glutamyl-transferase, testosterone and oestradiol were determined in plasma in non-diabetic males who had survived an acute myocardial infarction (AMI) before the age of 60. They also had serum levels of cholesterol below 7.0 mmol/l 1 year after the AMI. On the basis of diastolic blood pressure they were subdivided into 2 groups with diastolic blood pressures below 90 mm Hg (n = 39), and with or above 95 mm Hg (n = 21) and then compared with an age-matched male non-diabetic reference group (n = 32). There were no significant differences in the levels of HDL cholesterol, gamma-glutamyl-transferase, and sex hormones between the AMI groups and the reference group. Reduced plasma levels of apo A-I were found in the AMI groups.
Atherosclerosis 1986 Jan
PMID:Low serum apolipoprotein A-I in acute myocardial infarction survivors with normal HDL cholesterol. 308 Oct 12

Concentrations of serum lipoprotein lipids and apolipoproteins A-I, A-II and B were determined 3-6 months after myocardial infarction in 116 males below the age of 45 and in 116 age-matched controls. Among single variables the sum of cholesterol concentration in VLDL and LDL divided by the HDL cholesterol level was the best discriminator between patients and controls. The concentrations of serum triglycerides, apolipoprotein B, VLDL triglycerides and cholesterol, serum cholesterol, HDL cholesterol and LDL triglycerides, in that order, were better discriminators than was LDL cholesterol level. Among variables reflecting HDL concentration and composition HDL cholesterol was the best discriminator followed by HDL2 cholesterol, apolipoprotein A-I and the HDL cholesterol/apolipoprotein A-I ratio. Multivariate analysis indicated independent significance of elevated VLDL lipid and LDL cholesterol concentrations, and a decreased HDL cholesterol concentration, in relation to MI. The present data suggest that a disturbed triglyceride metabolism, in addition to elevated LDL and decreased HDL cholesterol levels, has an independent and pathogenetic significance for MI at a young age.
Atherosclerosis 1986 Feb
PMID:Serum lipoproteins and apolipoproteins in young male survivors of myocardial infarction. 308 33

The major structural components of high density lipoproteins were determined in the sera of 638 male employees aged 40 years and older. It was demonstrated that the HDL apolipoprotein A-I/HDL cholesterol ratio as well as the HDL apolipoprotein A-II/HDL cholesterol ratio are similarly correlated to a cumulative score of established risk factors for atherosclerosis. Most important, however, is the finding that the correlation of these ratios to the risk factor rating of atherosclerosis is found in subgroups with normal or elevated HDL cholesterol values. Furthermore, it is shown that the relative content of apolipoproteins A-I and A-II in individual HDL is partly dependent on the plasma concentration of HDL cholesterol and triglycerides. It is concluded that HDL composition may have an additional predictive significance for the development of atherosclerosis.
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PMID:HDL apolipoprotein A-I and HDL apolipoprotein A-II concentrations in male company employees in Westphalia aged 40 years and older. 309 83

A variety of lipids, lipoprotein (Lp) lipids and APO-Lp were measured in 72 patients of both sexes suffering from cerebrovascular arteriopathy and compared with a control group matched for age and sex. The best discriminators by univariate analysis were serum concentrations of APO-AI, followed by APO-AII, high density lipoprotein phospholipids and HDL cholesterol (HDL-C). Low density lipoprotein cholesterol and serum APO-B values were lower in the patients than in the controls. With APO-AI only, patients and controls could be classified with 88-91% certainty. By combination of some of the variables which were selected by a stepwise discriminant analysis, several models were calculated resulting in 93-97% segregation of patients from controls. By multivariate analysis, APO-AI, APO-AII, HDL-C, and triglycerides in combination with the blood pressure or the body weight index were independent variables (in a mathematical sense). By comparing the present data with published results of previous studies it is concluded that cerebral atherosclerosis differs from other forms of atherosclerosis by several major risk indicators.
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PMID:Apolipoproteins AI, AII and HDL phospholipids but not APO-B are risk indicators for occlusive cerebrovascular disease. 309 38

Following a brief outline of current knowledge concerning atherosclerosis and its treatment, the authors describe the results obtained by treating with pantethine (900-1200 mg daily for 3 to 6 months) a series of 7 children and 65 adults suffering from hypercholesterolemia alone or associated with hypertriglyceridemia (types IIa and IIb of Fredrickson's classification). Pantethine treatment produced significant reduction of the better known risk factors (total cholesterol, LDL-cholesterol, triglycerides, and apo-B) and a significant increase of HDL-cholesterol (signally HDL2) and apolipoprotein A-I. The authors conclude with a discussion of these results and of the possible role of pantethine in the treatment of hyperlipoproteinemia, in view of its perfect tolerability and demonstrated therapeutic effectiveness.
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PMID:Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children. 309 91

Studies of the catalase and apolipoprotein A-I genes are pertinent to the understanding of human disease. Not only are these genes involved in acatalasemia and atherosclerosis, respectively, but they are also important gene markers for chromosome 11, deletions of which are involved in the development of Wilms tumor. We have used in situ hybridization to localize these genes to specific bands on chromosome 11. Hybridization with a catalase cDNA yielded a significant number of cells (38%) exhibiting label at band 11p13. A high percentage of metaphase cells (50%) hybridized with a human genomic fragment containing the gene for apolipoprotein A-I displayed labeling at 11q13.
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PMID:Localization of the human catalase and apolipoprotein A-I genes to chromosome 11. 310 17

Two DNA polymorphisms adjacent to the apolipoprotein A-I/C-III and insulin genes have been suggested to be associated with hypertriglyceridemia and increased risk of coronary heart disease. Using cloned apolipoprotein A-I and insulin gene probes, we determined the genotypes of 39 subjects from six different kindreds with familial clustering of hypertriglyceridemia, 20 additional unrelated subjects with hypertriglyceridemia, 39 patients with angiographically confirmed coronary heart disease (CHD) and 61 normolipemic control subjects. The S2 allele bearing an additional SstI restriction site in the apo A-I/C-III complex was found in 16% of healthy controls, 23% of patients with CHD and 62% (P less than 0.001 when compared to controls) of unrelated subjects with hypertriglyceridemia. Among CHD patients the S2 allele was present in 6 out of 14 hypertriglyceridemic patients but only 3 out of 25 normotriglyceridemic patients (P less than 0.05). The S2 allele was present in 64% of subjects from kindreds with hypertriglyceridemia but this allele did not determine the occurrence of hyperlipidemia. The frequencies of the large size or U allele of the polymorphic DNA region flanking the 5' end of the insulin gene in CHD patients (33%) and in controls (24%) were not significantly different. Neither of the polymorphisms studied was associated with changes in serum LDL or HDL cholesterol levels in patients with CHD or unrelated subjects with hypertriglyceridemia. The data suggest that, at least in the Finnish population, the S2 allele of the apolipoprotein A-I/C-III gene complex may serve as a genetic marker for hypertriglyceridemia, whereas both DNA polymorphisms studied are probably useless in determining individual risks of atherosclerosis.
Atherosclerosis 1987 Jul
PMID:DNA polymorphisms of apolipoprotein A-I/C-III and insulin genes in familial hypertriglyceridemia and coronary heart disease. 311 75


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