Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments on rats with hyperlipemia induced by carbohydrates have been shown that synthesis of apoprotein B by the liver and its relative content in very low-density proteins (VLDP) of the liver and blood increase. This is accompanied by accelerated metabolism of C-III in blood VLDP and by hyperinsulinemia suggesting that hyperinsulinemia may be regarded as one of the mechanisms by which there occurs hyperlipemia under high carbohydrate diets.
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PMID:[Etiologic mechanisms of carbohydrate-induced hyperlipemia]. 702 Jul 94

New aspects in the pathogenesis and diagnosis of familial dysbetalipoproteinemia are discussed, including the clarification of the chemical basis of the polymorphism of apoprotein E, the allelic nature of the primary isoforms of the protein, the relationship of the abnormality of apoprotein E to the accumulation of remnant lipoproteins in dysbetalipoproteinemia and in persons carrying the trait for abnormal apoprotein E, and the pathogenesis of hyperlipidemia in this disorder. The related clinical features of dysbetalipoproteinemia are included in the discussion.
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PMID:Familial dysbetalipoproteinemia. New aspects of pathogenesis and diagnosis. 704 Aug 46

The effects of long term treatment with nicotinic acid on lipids, lipoproteins, and the plasma distribution of very low density lipoproteins (VLDL) apoprotein C (ApoC) subspecies were studied in 33 patients with types IIa (n = 9), IIb (n = 11), and IV (n = 13) hyperlipidemias. After 6 months of treatment, a significant decrease in triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol levels occurred. High density lipoprotein (HDL) cholesterol increased significantly by 31.1%, 41.8%, and 32.0% in types IIa, IIb, and IV, respectively (P less than 0.01 for all). A significant negative correlation existed between changes in HDL cholesterol and triglycerides (r = -0.613; P less than 0.02) in all groups studied. Therapy also produced changes in VLDL, LDL, and HDL protein concentrations. VLDL protein decreased from 20.9 +/- 3.9 to 15.2 +/- 1.0 mg/dl (P less than 0.05) in type IIa. In types IIb and IV, mean VLDL protein decreased from 44.7 +/- 8.2 to 27.1 +/- 3.9 mg/dl (P less than 0.001) and from 46.3 +/- 7.1 to 30.6 +/- 4.9 mg/dl (P less than 0.001), respectively. LDL protein decreased significantly, and HDL protein increased in type IIa only. Gel isoelectric focusing of VLDL before and after nicotinic acid in types IIb and IV hyperlipidemia produced a significant increase in the VLDL ApoC-II component with simultaneous decreases in the total VLDL ApoC-III subspecies. This resulted in increases in the ApoC-II to ApoC-III area ratio from 0.50 +/- 0.1 to 1.02 +/- 0.2 (P less than 0.001) in type IIb and from 0.62 +/- 0.07 to 0.88 +/- 0.13 (P less than 0.01) in type IV, respectively. The ApoE subspecies and the ApoE-III to ApoE-II area ratio did not change significantly. Our results show that nicotinic acid produces a significant improvement in the lipoprotein profiles of these patients.
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PMID:Effects of nicotinic acid therapy on plasma lipoproteins and very low density lipoprotein apoprotein C subspecies in hyperlipoproteinemia. 707 97

Patients with renal functional impairment are prone to develop hypertension and hyperlipidemia, and both abnormalities tend to occur already at an early stage of kidney disease. In 18 patients with mild renal disease (glomerular filtration rate 65 +/- 5 ml/min) and hypertension (mean blood pressure 126 +/- 4 mm Hg), the effect of six weeks of treatment with the loop-diuretic muzolimine on serum lipoproteins was assessed. Compared to placebo values, the diuretic significantly increased serum low-density lipoprotein cholesterol (LDL-C) and apoprotein B (+ 18 and 11%, respectively, P less than 0.005) in 13 men or postmenopausal women, but not in 5 premenopausal women. Serum high-density lipoprotein cholesterol (HDL-C), and total triglycerides or lipoprotein triglyceride fractions were not consistently changed in both subgroups. Thus, the ratio LDL-C/HDL-C was increased from 3.2 +/- 0.3 to 3.9 +/- 0.3 (P less than 0.05) in the men or postmenopausal women, while no such tendency occurred in the premenopausal women (4.1 +/- 0.6 to 3.7 +/- 0.6). Changes in serum LDL-C were not associated with hemoconcentration or alterations in carbohydrate metabolism and were not related to variations in serum potassium or blood pressure. Increased serum levels of the atherogenic LDL-C fraction during diuretic treatment in men or postmenopausal women with renal disease may represent a potentially undesirable effect, particularly since such patients may tend to have hyperlipidemia in the untreated state.
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PMID:Serum lipoproteins in patients with mild renal disease treated with the diuretic muzolimine. 715 18

The dynamics of human apoE metabolism were explored by examining the effects of alimentary lipemia and postheparin lipolysis on the plasma level and lipoprotein distribution of apoE. In the studies of alimentary lipemia, fasting and postprandial plasma samples were obtained from five normal adult males, each of whom drank 100 g of corn oil. Although no change in the plasma concentration of apoE accompanied alimentary lipemia, a major redistribution of apoE among lipoproteins occurred. The portion of apoE associated with triglyceride-rich lipoproteins as assessed by agarose column chromatography increased by a mean of 44%. Furthermore, in the two subjects in whom multiple postprandial samples were taken, there were striking linear correlations between plasma triglyceride concentrations and the fraction of apoE in triglyceride-rich lipoproteins (r = 0.96 and 0.73). In contrast, the plasma concentration of apoE fell in each of the seven studies of postheparin lipolysis. The fall averaged 17% of the control plasma apoE level. In hypertriglyceridemic patients, the decline in plasma triglyceride concentration preceded the decline in apoE concentration, suggesting that the decline in apoE was due to removal of remnants of triglyceride-rich lipoproteins. Lipoprotein fractionation demonstrated substantial loss of apoE from triglyceride-rich lipoproteins; the data suggested that this loss of apoE from triglyceride-rich lipoproteins was due both to removal of apoE from plasma and to transfer of apoE to an HDL fraction. During the recovery phase, as plasma triglyceride levels rose, opposite changes occurred: the plasma apoE level rose, apoE in triglyceride-rich lipoproteins increased in concentration, and apoE in HDL decreased in concentration. Furthermore, it became apparent during the recovery phase that apoE in triglyceride-rich lipoproteins was composed of two discrete subfractions. The first subfraction consisted of apoE on larger, probably recently synthesized lipoproteins; the second consisted of apoE on much smaller lipoproteins. These studies provide evidence in intact humans for a dynamic traffic of apoE between triglyceride-rich lipoproteins and high density lipoprotein. This traffic is a prominent phenomenon of normal alimentary lipemia and of lipolysis. By modulating the lipoprotein distribution of apoE, it probably plays a key functional role in lipoprotein metabolism.-Blum, C. B. Dynamics of apolipoprotein E metabolism in humans.
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PMID:Dynamics of apolipoprotein E metabolism in humans. 716 60

The body of evidence incriminating genetic factors in the etiology of CHD includes familial clustering of cases, with or without major hyperlipidemia; genetic influence on serum lipids levels in the general population; effect of genes belonging to normal polymorphisms on serum lipid levels and their variability; atherogenic effect of the genetically determined Lp(a) lipoprotein; and genetic influence on HDL apoproteins. Recent findings concerning the inherited apoE variation and genetic control of LDL cell membrane receptor activity in the general population are potentially of considerable interest. An improved understanding of the interaction between the products of "susceptibility genes" and environmental/dietary factors is important for attempts to prevent or delay the manifestations of atherosclerosis.
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PMID:The genetics of the hyperlipidemias and coronary artery disease. 716 16

1. Significant positive correlations were found between the lipoprotein lipase and hepatic lipase activities of post-heparin plasma samples and plasma high-density-lipoprotein (HDL) cholesterol concentrations in 21 children with hyperlipidaemia and six normal adult males. 2. A significant positive correlation was also observed between the two lipase activities and the ratio of HDL cholesterol to apoprotein AI (apo AI) concentrations. 3. These findings provide further evidence that a significant proportion of HDL and possibly the HDL, subfraction is formed during the clearance of triglyceride-rich lipoproteins.
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PMID:Relationship between plasma high-density lipoprotein concentrations and lipoprotein lipase and hepatic lipase activities in children with hyperlipidaemia. 726 47

The effect of 2 to 3 weeks of 73% sucrose feeding and intestinal sucrose infusion upon intestinal lipoprotein formation was studied in mesenteric lymph cannulated female rats. Lymph lipoprotein fractions were analyzed for lipid and apoprotein content and were compared to chow-fed control rats. The sucrose regimen increased mesenteric lymph triglyceride output by 54%, the increase being confined to the very low-density lipoprotein fraction. Sucrose infusion in chow-fed control rats did not increase lymph triglyceride transport when compared to infusion of a glucose polymer. Unesterified cholesterol output in whole lymph was stimulated by sucrose by 76%. Both the d greater than 1.006 and d less than 1.006 g/ml fractions of lymph were found to have an increase in unesterified cholesterol output. Since no difference in the chemical composition of very low-density lipoproteins in the two groups of animals was detected, sucrose appeared to increase the number of very low-density lipoprotein particles secreted by the intestine. Sucrose did not alter the relative proportions of apo A1, apo A4, apo ARP, and total C peptides present in very low-density lipoproteins. However, differences in the proportion of apo C subunits after sucrose were detected by isoelectric focusing with a pronounced increase in the apo CIII0 peak. The present studies demonstrate that the intestine participates in changes in lipoprotein formation and metabolism that accompany experimental sucrose induced hyperlipidemia.
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PMID:Effect of sucrose on intestinal very low-density lipoprotein production. 736 55

Apolipoprotein (apo) E-deficient transgenic mice develop marked hyperlipidemia and progressive atherosclerotic lesions. To explore whether oxidative modification of lipoproteins is involved in atherogenesis in this murine model, we performed extensive immunocytochemical studies. Atherosclerotic lesions ranging from early fatty streaks to very advanced plaques were examined from the aortic valve region and the thoracic and abdominal aorta. Using guinea pig antisera against malondialdehyde (MDA)-lysine and 4-hydroxynonenal-lysine, two epitopes generated during the oxidative modification of low-density lipoprotein (LDL), we demonstrated the presence of these "oxidation-specific epitopes" in atherosclerotic lesions. In early lesions, oxidation-specific epitopes were found predominantly in macrophage-rich areas, whereas diffuse extracellular staining predominated in necrotic areas of advanced lesions. We have previously shown that autoantibodies against MDA-lysine are present in the circulation of humans and rabbits and that the immunoglobulin fraction extracted from their lesions contains autoantibodies against several "oxidation-specific" epitopes. Sera from apoE-deficient mice also contained circulating autoantibodies to MDA-lysine, and both early and advanced lesions were rich in murine immunoglobulins. Titers of serum autoantibodies were significantly higher in apoE-deficient mice than in C57BL/6 mice. Autoantibodies in murine plasma recognized MDA-lysine epitopes in atherosclerotic lesions of rabbits, and the immunostaining was competitively inhibited by excess human MDA-LDL. Similar findings were obtained by competitive radioimmunoassay. Finally, a morphometric technique was developed and tested in these mice that allows a quantitative assessment of aortic atherosclerosis. These findings suggest that in apoE-deficient mice, lipoprotein oxidation is involved in atherogenesis and that these transgenic mice constitute an appropriate model with which to study the antiatherogenic effect of antioxidant intervention.
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PMID:ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis. Demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum. 751 33

Approximately 1% to 2% of persons in the general population are homozygous for a lipoprotein receptor-binding defective form of apoE (apoE2/2). However, only a small percentage (2% to 5%) of all apoE2/2 homozygotes develop type III hyperlipoproteinemia. Interaction with other genetic and environmental factors are required for the expression of this lipid abnormality. We sought to investigate the possible role of LPL gene mutations in the development of hyperlipoproteinemia in apoE2/2 homozygotes and in apoE2 heterozygotes. As a first step, we performed DNA sequence analysis of all 10 LPL coding exons in 2 patients with the apoE2/2 genotype who had type III hyperlipoproteinemia and identified a single missense mutation (Asn 291-->Ser) in exon 6 of the LPL gene. The mutation was then found in 5 of 18 patients with type III hyperlipoproteinemia who had the apoE2/2 genotype (allele frequency = 13.9%; P < or = 7.4 x 10(-5)) and 6 of 22 hyperlipidemic E2 heterozygous patients with the apoE3/2 and E4/2 genotype (allele frequency = 13.6%; P = 2.2 x 10(-5)). In contrast, this mutation was found in only 3 of 230 normolipidemic controls (allele frequency = 0.7%). In vitro mutagenesis studies revealed that the Asn 291-->Ser mutant LPL had approximately 60% of LPL catalytic activity and approximately 70% of specific activity compared with wild-type LPL. The heparin-binding affinity of the mutant LPL was not impaired. Our data suggest that the Asn 291-->Ser substitution is likely to be a significant predisposing factor contributing to the expression of different forms of hyperlipidemia when associated with other genetic factors such as the presence of apoE2.
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PMID:Patients with apoE3 deficiency (E2/2, E3/2, and E4/2) who manifest with hyperlipidemia have increased frequency of an Asn 291-->Ser mutation in the human LPL gene. 758 46


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