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 significance of high density lipoproteins in the etiology of clinical complications to atherosclerosis has recently received increased attention. The levels of the major apolipoprotein in high density lipoproteins, apoA-I, have been determined in patients who had had an acute myocardial infarction, and compared with a cholesterol-matched and a randomly selected control group. ApoA-I levels were lower in the patients than in the control groups. ApoA-I levels were also lower in smokers than in non-smokers. The difference between patients and control groups persisted even when the groups were stratified according to smoking habits. This suggests that low levels of apo-A-I as well as alphalipoprotein cholesterol are additional characteristics of the infarction patients, even when the established risk factors, smoking and hyperlipidemia are taken into account.
Atherosclerosis 1980 May
PMID:Serum apolipoprotein levels in relation to acute myocardial infarction and its risk factors. Apolipoprotein A-I levels in male survivors of myocardial infarction. 738 77

Apolipoprotein A-I, A-II and apoD are all primarily found in the density region d > 1.063 g/ml. In the present study the serum apoD level was determined by electroimmunoassay in a random population sample of middle-aged men (n = 76). The mean level was 0.075 g/l with a standard deviation of 0.017. The apoD level was also determined in a group of patients, in the same age range, with sustained acute myocardial infarction (n = 25). The patients were compared with the random population sample and with a control group matched to the patients with regard to age, serum cholesterol level and body weight index. There was no difference in apoD level between patients and either control group. This is in contrast with the earlier reported low apoA-I, A-II as well as alphalipoprotein cholesterol levels in the same patient group.
Atherosclerosis 1980 Dec
PMID:Serum apolipoprotein levels in relation to acute myocardial infarction and its risk factors--determination of apolipoprotein D. 745 6

We report a 39-year-old Japanese man with HDL and apoA-I deficiency as well as data from members of his family. Corneal opacity and a stomatocyte were found but not tonsillar hypertrophy, xanthomas, or splenomegaly. His serum HDL cholesterol, apoA-I, apoA-II, and LDL cholesterol levels were t mg/dL, < 3 mg/dL, 6 mg/dL, and 175 mg/dL, respectively. Plasma triglyceride, phospholipid, apoB, apoC-III, and apoE levels were all within normal limits. Lecithin:cholesterol acyltransferase activity was half of normal, while lipoprotein lipase and hepatic triglyceride lipase activities were within normal limits. ApoA-I deficiency was confirmed by combined isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by an immunoblotting method. We surveyed the apoA-I gene of the patient and five of his family members by direct sequencing after amplification by polymerase chain reaction and found a codon 8 nonsense mutation (TGG --> TAG, Trp --> stop) in exon 3 of the apoA-I gene. The results of a pedigree analysis by DNA sequencing and restricted fragment length polymorphism (Sty I) were consistent with an autosomal codominant trait. Coronary angiography was performed to evaluate coronary atherosclerosis, but no significant luminal narrowing was detected. An intracoronary ultrasound study showed mild intimal hyperplasia in segment 6. In summary, this is a case of apoA-I deficiency without evidence of coronary heart disease.
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PMID:A new case of apoA-I deficiency showing codon 8 nonsense mutation of the apoA-I gene without evidence of coronary heart disease. 758 66

HDLs are heterogeneous in their apolipoprotein composition. Apolipoprotein (apo) A-I and apoA-II are the major proteins found in HDL and form the two major HDL subclasses: those that contain only apoA-I (LpA-I) and those that contain both apoA-I and apoA-II (LpA-I:A-II). Substantial evidence indicates that these two subclasses differ in their in vivo metabolism and effect on atherosclerosis, with LpA-I the more specifically protective subfraction against atherosclerosis. The purpose of this study was to investigate the effect of apoA-I and apoA-II production and catabolism on plasma LpA-I and LpA-I:A-II levels. Fifty normolipidemic subjects (those with HDL cholesterol levels in the top and bottom tenth percentiles were excluded) underwent kinetic studies with radiolabeled apoA-I and apoA-II, and the kinetic parameters of apoA-I and apoA-II were correlated with LpA-I and LpA-I:A-II levels. ApoA-I levels were strongly correlated with apoA-I residence times and less strongly correlated with apoA-I production rates. In contrast, apoA-II levels were correlated only with apoA-II production rates and not with apoA-II residence times. Levels of apoA-I in LpA-I were correlated with apoA-I residence times, whereas levels of apoA-I in LpA-I:A-II were correlated primarily with apoA-II production rates. The fraction of apoA-I in LpA-I was highly inversely correlated with apoA-II production rate (r = -.67, P < .001). In multiple regression analysis, apoA-II production rate was the most significant independent variable determining percent apoA-I in LpA-I among all the kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoprotein A-II production rate is a major factor regulating the distribution of apolipoprotein A-I among HDL subclasses LpA-I and LpA-I:A-II in normolipidemic humans. 774 39

Concentrations of plasma high density lipoprotein (HDL) are inversely correlated with atherosclerotic coronary artery disease. The two most abundant protein constituents of HDL are apolipoproteins A-I and A-II (apoA-I and apoA-II). ApoA-I is required for assembly of HDL and, when overexpressed in transgenic mice, confers resistance to early atherosclerosis. The present studies reveal that transgenic mice that overexpress mouse apoA-II had elevated HDL-cholesterol concentrations but, nevertheless, exhibited increased atherosclerotic lesion development as compared to normal mice. The HDL in the transgenic mice was larger and had an increased ratio of apoA-II to apoA-I. Thus, both the composition and amount of HDL appear to be important determinants of atherosclerosis.
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PMID:Atherosclerosis in transgenic mice overexpressing apolipoprotein A-II. 833 12

Pericardial fluid paraoxonase activity was compared with 3 biochemical markers of atherosclerosis (HDL, LDL/HDL ratio and Apolipoprotein A-I) and a significant association was found. When the paraoxonase activity in pericardial fluid samples was separated into 2 groups according to the degree of coronary atherosclerosis (slight and severe), most of the cases showing low levels of paraoxonase activity also showed severe coronary atherosclerosis. In addition, paraoxonase activity in pericardial fluid was found to be statistically correlated with HDL levels, which agrees with the results reported in serum.
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PMID:Paraoxonase activity in human pericardial fluid: its relationship to coronary artery disease. 839 Aug 52

Since plasma high density lipoprotein (HDL) concentrations are inversely related to the development of atherosclerosis, induction of HDL after pharmacological treatment is considered of benefit. To study whether currently used hypolipidemic drugs affect HDL metabolism by modulating the expression of genes involved in HDL metabolism, liver and intestinal apolipoprotein (apo) AI, apo-AII and apo-AIV gene expression was evaluated in rats treated with different classes of hypolipidemic drugs, and correlated to the changes in plasma lipid and apolipoprotein concentrations. In rats, the most pronounced hypolipidemic effects were observed after treatment with the fibrates clofibrate and fenofibrate, which lowered plasma lipid, apo-AI and apo-AIV concentrations. This decrease was accompanied by lowered liver apo-AI, apo-AII and apo-AIV mRNA levels. None of the other compounds tested affected plasma cholesterol, whereas probucol and simvastatin decreased plasma triglyceride concentrations. Apo-AI and apo-AII mRNA remained constant after nicotinic acid and probucol, whereas liver apo-AIV mRNA levels decreased. Cholestyramine increased hepatic apo-AI and apo-AII, but not apo-AIV mRNA levels. Simvastatin treatment increased apo-AI mRNA nearly threefold, whereas apo-AII and apo-AIV decreased by more than 50%. Similarly as after cholestyramine, the alteration in hepatic apo-AI mRNA levels did not result in changed plasma apo-AI concentrations. Remarkably, none of the drugs tested significantly affected intestinal apolipoprotein mRNA levels. These results indicate that hypolipidemic drugs may act on plasma lipoprotein metabolism by regulating apolipoprotein gene expression. Further studies in humans and primates are therefore warranted.
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PMID:Effects of hypolipidemic drugs on the expression of genes involved in high density lipoprotein metabolism in the rat. 868 57

Apolipoprotein A-I, a protein produced mainly by hepatocytes, is of major importance in prevention of atherosclerosis. Its serum level varies according to the degree of liver fibrosis and the mechanism of this regulation is unknown. The aim of this study was to investigate the role of extracellular matrix in the regulation of apolipoprotein A-I by the liver. Primary mouse hepatocytes were cultured on different extracellular matrix components. The apolipoprotein A-I mRNA level was quantified in these different culture conditions by a sensitive quantitative RT-PCR procedure and compared according to the extracellular matrix component used as substrate. A significant decrease in the apolipoprotein A-I mRNA level was observed when cells were plated on fibronectin by comparison with cells cultured on all other components. Potential binding of apolipoprotein A-I to the different matrix components was also studied in vitro. We demonstrated that apolipoprotein A-I significantly bound to fibronectin in a concentration-dependent, saturable and specific manner. Thus, fibronectin, a major liver extracellular matrix component, can interact with apolipoprotein A-I both by downregulating its mRNA level in liver cells and by binding this molecule after its secretion in the extracellular space. Since fibronectin is the first matrix component to be produced in excess and deposited in liver fibrosis, it could be involved in the decrease in serum apolipoprotein A-I in alcoholic patients with liver fibrosis and cirrhosis.
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PMID:Role of liver extracellular matrix in transcriptional and post-transcriptional regulation of apolipoprotein A-I by hepatocytes. 882 8

A method is described for the large scale preparation of reconstituted high density lipoproteins (rHDL) suitable for therapeutic use. Apolipoprotein A-I (apoA-I was isolated from precipitates obtained by cold ethanol fractionation of human plasma. This process includes several steps for virus removal and virus inactivation, among them pasteurization. Reconstitution of lipoprotein particles was performed by cholate dialysis using soybean phosphatidylcholine as the lipid source. An apoA-I:lipid ratio of 1:150 (mol:mol) was obtained. Redissolved rHDLs were disc-shaped particles resembling nascent HDL, as assessed by electron microscopy. The method was optimized for low content of free apoA-I protein as well as the low concentration of free lipid. The product was stabilized by lyophilization in the presence of sucrose. In vitro studies show potential effects it the prevention of gram-negative septic shock and in the inhibition of atherosclerosis.
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PMID:Production and characterization of a reconstituted high density lipoprotein for therapeutic applications. 891 58

Apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) represent 80 90% of the protein content of high density lipoproteins (HDL). Previously we have identified a Finnish family with an apo A-I variant (Lys107-->0) associated with reduced plasma HDL cholesterol level and decreased lipoprotein (Lp)(AI w AII) concentration compared to unaffected family members. To determine the in vivo metabolism of apo A-I and apo A-II in the carriers of apo A-I (Lys107-->0) variant we radioiodinated normal apo A-I with 125I and apo A-II with 131I and compared the kinetic data of two heterozygous apo A-I(Lysl07-->0) patients (HDL cholesterol leves 0.31 and 0.69 mmol/l) to that of eight normolipidemic, healthy control subjects. Plasma radioactivity curves of 125I-labelled normal apo A-I of the patients demonstrated accelerated clearance of apo A-I compared to control subjects. In the two patients the fractional catabolic rates (FCR) of apo A-I were 0.347/day and 0.213/day, respectively, while the mean FCR of apo A-I of the control subjects was 0.151 +/- 0.041/day. Similarly, the plasma decay curves of the 131I-labelled apo A-II showed more rapid clearance of apo A-II in the two patients than in control subjects. The FCR of apo A-II in the two patients were 0.470/day and 0.234/day, while the mean FCR of apo A-II in control subjects was 0.154 +/- 0.029/day. The calculated production rates of apo A-I were similar in patients and in control subjects, and the production rates of apo A-II were significantly higher in patients than in control subjects. Our results show that the Lp(AI w AII) deficiency in patients with the apo A-I(Lys107-->0) is associated with increased fractional catabolic rates of normal apo A-I and apo A-II, while the production rates of these apolipoproteins are normal (apo A-I) or slightly increased (apo A-II).
Atherosclerosis 1997 Feb 10
PMID:In vivo metabolism of apo A-I and apo A-II in subjects with apo A-I(Lys107-->0) associated with reduced HDL cholesterol and Lp(AI w AII) deficiency. 905 Jul 78


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