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)

Apolipoprotein A-I (apoA-I) spontaneously associates with dimyristoylphosphatidylcholine (DMPC) liposomes to form discoidal high-density lipoprotein (HDL) recombinants. The uptake of cholesterol by this model HDL was studied by incubation with Celite-dispersed cholesterol. Separation of the resulting complexes by gradient centrifugation and gel filtration showed a heterogeneous distribution of particle size and composition as a consequence of the disruption and rearrangement of the recombinants. Quantitation of the amount of cholesterol taken up gave values between about 28 and 40 mol% cholesterol for the fractions within the protein peaks; the fractions with the lowest DMPC/apoA-I ratios had the lowest cholesterol contents. In another set of experiments, the association of apoA-I with DMPC-cholesterol liposomes was shown to result in complexes with characteristics similar to those obtained by the cholesterol-uptake experiments. Low concentrations of cholesterol in the liposomes enhanced the rate of lipid-protein association, but larger amounts decreased the yield of complexes by making the process thermodynamically and kinetically unfavorable. The enthalpy of recombinant formation increased with decreasing lipid/protein ratio and increasing cholesterol content, and became endothermic at about 23 mol% cholesterol. The effect of cholesterol on the thermal properties of HDL recombinants suggests that cholesterol is partially excluded from the boundary region adjacent to apoA-I. It is concluded that discoidal HDL recombinants, as a model for 'nascent' HDL, can acquire substantial amounts of cholesterol, which may be of great physiological importance for the reverse cholesterol transport and prevention of atherosclerosis.
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PMID:Incorporation of cholesterol into apolipoprotein A-I-dimyristoylphosphatidylcholine recombinants. 313 42

Seventeen patients with familial hypercholesterolemia (9 males and 8 females) were treated with 1000 mg deoxycholic acid or placebo daily during 2 weeks in a double-blind, randomised cross-over fashion. A wash-out period was held between the two periods of therapy. Clinical chemical parameters, lipoprotein cholesterol and apolipoproteins were measured before and after each period. Low density lipoprotein cholesterol was reduced by 7.5% and LDL-apo B by 5.6%. Only the latter change was significantly different from the corresponding changes in the placebo period (P less than 0.05). High density lipoprotein cholesterol did not change. Apolipoprotein A-I decreased by 4% (P less than 0.05). Apolipoprotein A-II did not change. While taking deoxycholic acid, most patients had abdominal discomfort and/or diarrhoea. The serum transaminases increased in 7 patients taking this drug and in none while taking a placebo. We conclude that this therapy is of little value in hypercholesterolemic patients.
Atherosclerosis 1986 Oct
PMID:Effect of deoxycholic acid on lipoprotein and apolipoprotein levels in patients with familial hypercholesterolemia. 353 14

Serum lipid and apolipoprotein concentrations were measured in 37 male survivors of cerebral infarction (CI) and in 30 healthy controls. Both groups had similar total cholesterol levels, but the HDL-cholesterol level was significantly lower and the serum triglyceride level was significantly higher in the CI patients than in the controls. The ApoB level was significantly higher in the CI patients but there was no significant difference between the 2 groups in the levels of the other apolipoproteins (ApoA-I, A-II, C-II, C-III, and E). The HDL-cholesterol/ApoA-I ratio was significantly lower in the CI patients. Both the VLDL-triglyceride and VLDL-cholesterol levels were higher in the CI patients but the VLDL-cholesterol especially its cholesterol ester level was conspicuously high. A population of VLDL particles that bound to heparin on heparin-Sepharose columns was increased in the CI patients. We suggest that cholesterol ester is excessively transferred from HDL to VLDL during the disturbed catabolism of VLDL in CI patients.
Atherosclerosis 1987 Nov
PMID:Lipoprotein abnormalities in survivors of cerebral infarction with a special reference to apolipoproteins and triglyceride-rich lipoproteins. 368 76

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

Apolipoprotein A-I (apo A-I) is the major protein constituent of high-density lipoprotein (HDL). The study of the apo A-I gene is of interest because plasma levels of HDL have been inversely correlated with the development of coronary artery disease and because polymorphisms related to this gene have been associated with hypertriglyceridaemia and premature atherosclerosis. We have recently isolated and characterized the human apo A-I gene and have shown that apo A-I and apolipoprotein C-III (apo C-III) genes are physically linked and that a polymorphism (of unknown frequency in the general population) of the apo A-I gene is inherited as a mendelian trait linked to premature atherosclerosis in an affected family (not the same polymorphism as has previously been reported to be associated with hypertriglyceridaemia). Here we report that this polymorphism is due an at least 6.5-kilobase (kb) DNA insertion in the coding region of the apo A-I gene and that there is no detectable alteration (as determined by limited genomic blotting analysis) of the apo C-III gene of these patients.
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PMID:A DNA insertion in the apolipoprotein A-I gene of patients with premature atherosclerosis. 631 45

The in vivo effects of the hypolipidemic drug clofibrate (0.5 mmol/kg body wt daily p.o. for 7 days) on serum lipids and apolipoproteins have been studied in male rats. Clofibrate caused an increase in liver weight without affecting body weight. Triglyceride, total and free cholesterol and HDL cholesterol were decreased in sera of clofibrate-treated rats. The relative abundance, and accordingly the absolute quantities, of the polyunsaturated fatty acids linoleic (18:2), linolenic (18:3) and docosahexenoic (22:6) in serum triglyceride decreased in response to clofibrate treatment. The concentrations of serum apolipoproteins A-I, B and C-III were reduced in clofibrate-treated rats. The apolipoprotein E level was not altered. The distribution of apolipoproteins A-I, B, C-III and E between heparin-Mn supernatant and precipitate were unaffected. The unchanged C-III distribution indicates unaltered intravascular VLDL catabolism. Concurrent reductions in serum HDL cholesterol and ApoA-I in clofibrate-treated rats suggest a diminished production of lipoprotein particles containing ApoA-I. Reductions in serum ApoB and in the mass ratio of serum triglyceride to ApoB indicate a decrease in the number and size, respectively, of circulating triglyceride-rich lipoprotein particles. These observations suggest that the hypolipidemic effect of clofibrate in the normolipemic rat is caused mainly by diminished hepatic secretion, rather than by enhanced catabolism, of triglyceride-rich lipoproteins.
Atherosclerosis 1983 Dec
PMID:Alterations in rat serum lipids and apolipoproteins following clofibrate treatment. 641 47

Apolipoprotein A-I (apo A-I), the major apolipoprotein in human high density lipoproteins, is involved in the disease atherosclerosis. Cloned apo A-I cDNA (pA1-3) was used as a probe in chromosome mapping studies to detect the human apo A-I structural gene sequence in human-Chinese hamster cell hybrids. Southern blot analysis of 13 hybrids localized the gene to human chromosome 11. Confirmation of the chromosomal assignment was obtained by analysis of a hybrid (J1) containing a single human chromosome, no. 11. Regional mapping was achieved by using deletion subclones of J1 that localized the human apo A-I structural gene to the region 11q13 leads to qter. Since the human apolipoprotein C-III (apo C-III) structural gene is closely linked to apo A-I, it can be assigned to the same region on the long arm of chromosome 11. By extension of methods previously described, it now appears possible to carry out fine-structure analysis of this and related gene regions on chromosome 11 and to study the biochemical concomitants of these genes and of genes on other chromosomes for analysis of their role in atherosclerosis.
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PMID:Localization of the structural gene for human apolipoprotein A-I on the long arm of human chromosome 11. 642 Jul 90

A lipoprotein species with ultracentrifugal flotation rates (F0(1.20) 9-28) intermediate to high density lipoproteins (HDL, F0(1.20) 0-9) and low density lipoproteins (LDL, F0(1.20) 28-56) found in the plasma of certain pedigreed baboons fed an atherogenic diet was studied by gradient gel electrophoresis (GGE) and ultracentrifugal techniques. These lipoproteins were found to be heterogeneous in size (125-220 A) and hydrated density (1.028-1.080 g/ml). The major apolipoprotein in all density subfractions of the F0(1.20) 9-28 lipoproteins exhibited the molecular weight (2.8 X 10(4) daltons) and immunochemical properties of apolipoprotein A-I (apoA-I). Protein corresponding to apolipoprotein E (apoE, 3.5 X 10(4) daltons) was observed primarily in the less dense subspecies of F0(1.20) 9-28 lipoproteins. Some low molecular weight (1.8 X 10(4), 1.3 X 10(4), and 1.1 X 10(4) daltons) apolipoproteins were also detected. At low serum F0(1.20) 9-28 lipoprotein concentrations, only the smaller, more dense, protein-rich species were present; at higher F0(1.20) 9-28 concentrations, the larger, less dense species were observed in addition to the small species. The HDL of pedigreed baboons in families with and without serum F0(1.20) 9-28 lipoproteins were also characterized. The HDL of both groups of progeny consisted of a similar set of 5 subpopulations designated HDL-I through HDL-V determined by GGE. HDL-I, consisting of material 100-125 A in size, was the major HDL subpopulation. ApoA-I was the major protein moiety in all HDL subpopulations; none contained apoE. Baboons in families with F0(1.20) 9-28 lipoproteins had more HLD-I (292 +/- 80 mg/dl vs. 235 +/- 55 mg/dl) and less HDL-II (86 +/- 22 mg/dl vs. 135 +/- 34 mg/dl) than baboons in families without F0(1.20) 9-28 lipoproteins; both groups showed identical total HDL concentrations (446 +/- 90 mg/dl and 444 +/- 49 mg/dl, respectively). Among those baboons in families with F0(1.20) 9-28 lipoproteins, there was an inverse correlation between F0(1.20) 9-28 concentration and total HDL, HDL-I and HDL-II concentrations, indicating a possible metabolic relationship between these HDL subpopulations and the F0(1.20) 9-28 species.
Atherosclerosis 1984 Jul
PMID:Characterization of HDL and lipoproteins intermediate to LDL and HDL in the serum of pedigreed baboons fed an atherogenic diet. 646 14

The effects of colestipol (30 grams/day), niacin (7.3 grams/day), and diet on blood lipids and apolipoproteins after one year of therapy are reported. Men selected on the basis of previous coronary artery bypass surgery were randomly assigned to drug or control treatments in an angiographic study of atherosclerosis progression and regression. In 14 men, drugs and diet produced the following changes: Baseline total cholesterol 245 mg/dl, triglyceride 189 mg/dl, and LDL cholesterol 164 mg/dl were decreased by 73 mg/dl (29%), 83 mg/dl (41%) and 69 mg/dl (40%) respectively. Baseline HDL cholesterol, 44 mg/dl was increased 13 mg/dl (33%). Baseline apolipoprotein B, 124 mg/dl and apolipoprotein C-III (heparin precipitate) 5.6 mg/dl were decreased 40 mg/dl (31%) and 2.4 mg/dl (41%) respectively. All these changes are significant, p less than 0.01. Apolipoprotein A-I and apolipoprotein C-III (heparin supernate) were not significantly changed. In the controls, placebo and diet produced no significant decrease in blood lipid or lipoproteins, with the exception that baseline apolipoprotein B, 111 mg/dl increased 18 mg/dl (12%), p less than 0.05.
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PMID:Combined therapy of niacin, colestipol, and fat-controlled diet in men with coronary bypass. Effect on blood lipids and apolipoproteins. 665 12

Apolipoprotein A-I was quantitated by electroimmunoassay in buffer-soluble fractions of both grossly normal intima and raised atherosclerosis lesions of the human aorta. The mean value for apolipoprotein A-I content in microgram/mg tissue dry weight of normal intima (12 cases) was 0.71 +/- 0.10 S.E. and of aortic plaques (19 cases) was 0.64 +/- 0.40 S.E. When compared to the buffer-extractable apolipoprotein B content measured in these same cases from both regions, the ratio of apolipoprotein B to apolipoprotein A-I was approximately 6. No apolipoprotein A-I was measurable in tunica media. Following differential ultracentrifugation into d less than 1.063, d 1.063-1.21 and d greater than 1.21 fractions, the distributions of recovered apolipoprotein A-I were, respectively: 1, 94 and 5% for normal intima, 19, 31 and 50% for plaques and 1, 89 and 10% for plasma. Characterization of a chromatographically purified d 1.063-1.21 or HDL density fraction from fatty-fibrous plaques demonstrated particles of between 60 and 120 A diameter, a characteristic apolipoprotein A-I band by SDS-polyacrylamide gel electrophoresis, and a precipitin peak closely migrating with that for plasma HDL by two-dimensional immunoelectrophoresis. The d greater than 1.21 density fraction from plaques isolated by affinity chromatography on a Sepharose-anti-apolipoprotein A-I column contained small amounts of phospholipid but no measurable cholesterol. The d 1.063-1.21 density fraction from plaques showed a significant increase in percent free cholesterol and phospholipid contents and decrease in cholesteryl ester content relative to plasma HDL. This increase in free cholesterol could represent evidence for an anti-atherogenic mechanism wherein infiltrated HDL removes cholesterol together with phospholipid from the arterial wall.
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PMID:Lipoproteins containing apolipoprotein A-I extracted from human aortas. 680 57


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