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)

Plasma lipid/lipoprotein changes were monitored after a fat load (65 g fat per square meter body surface area) in six carriers of the apolipoprotein A-IMilano (A-IM) variant and six age- and sex-matched control subjects. The magnitude of postprandial lipemia, calculated as the area under the curve (AUC) described by plasma triglyceride (TG) level versus time, was threefold higher in the A-IM carriers; however, after correction for the different baseline TG levels, it was similar to control subjects. Moreover, the magnitude of postprandial lipemia was positively correlated with baseline TG in both A-IM carriers (r = 0.77) and control subjects (r = 0.80), indicating that fasting TGs are a major determinant of postprandial response in all subjects. Postprandial lipemia was also inversely correlated with high density lipoprotein (HDL) and HDL2 cholesterol in both groups (A-IM, r = -0.81 and -0.79; control subjects, r = -0.87 and -0.94). Different from those in control subjects, the plasma apo A-I levels in the A-IM carriers decreased progressively while apo B increased up to 4 hours but decreased thereafter. Postprandial rises of low density lipoprotein TG but not of HDL-TG AUC were significantly higher in the A-IM carriers, even after normalization for the different fasting concentrations. These data show that the low plasma HDL levels of A-IM carriers, which are secondary to a primary structural alteration of the major HDL apolipoprotein, are associated with elevated fasting and postprandial TG levels and an anomalous postprandial redistribution of TG among lipoprotein classes.
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PMID:Increased postprandial lipemia in Apo A-IMilano carriers. 846 88

Lipoprotein metabolism is altered in the majority of patients with renal insufficiency and renal-failure, but may not necessarily lead to hyperlipidemia. The dyslipoproteinemia of renal disease has characteristic abnormalities of the apolipoprotein (apo) profile and lipoprotein composition. It develops during the asymptomatic stages of renal insufficiency and becomes more pronounced as renal failure advances. The qualitative characteristics of renal dyslipoproteinemia are not modified substantially by dialysis treatment. Patients with chronic renal disease may therefore be exposed to dyslipoproteinemia for long periods of time. The characteristic plasma lipid abnormality is a moderate hypertriglyceridemia. The alterations of lipoprotein metabolism affect both the apoB-containing very low-density and intermediate-density, and low-density lipoproteins and the apoA-containing high-density lipoproteins. The main underlying abnormality of lipoprotein transport is a decreased catabolism of the apoB-containing lipoproteins caused by decreased activity of lipolytic enzymes and altered lipoprotein composition. There is an increase of intact or partially metabolized, triglyceride-rich, apoB-containing lipoproteins with a disproportionate elevation of apoC-III and, to a lesser extent, apoE, resulting in a marked increase of the intermediate-density lipoproteins and an enrichment of triglycerides, apoC-III, and apoE in the low-density lipoproteins. In high-density lipoproteins there are decreases in the concentrations of cholesterol, apolipoproteins A-I and A-II, and the high-density lipoprotein-2 to high-density lipoprotein-3 ratio. These abnormalities result in a characteristic decrease of the apoA-I to apoC-III ratio and anti-atherogenic index apoA-I/apoB. The pathophysiologic links between the renal insufficiency and the abnormalities of lipoprotein transport are still poorly defined. Changes in the action of insulin on lipolytic enzymes, possibly mediated via increased levels of parathyroid hormone, have been suggested to play a contributory role. The clinical consequences of a defective lipoprotein transport may be related to the atherogenic character of lipoprotein abnormalities. Renal dyslipoproteinemia may contribute to the development of atherosclerotic vascular disease and progression of glomerular and tubular lesions with subsequent deterioration of renal function. Dietary and/or pharmacologic intervention may ameliorate the uremic dyslipoproteinemia, but the long-term clinical effects of such treatment have yet to be established.
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PMID:Lipoprotein metabolism and renal failure. 850 11

The nephrotic syndrome is characterized by reduced plasma albumin and colloid osmotic pressure (pi). Infusion of dextran or albumin reduces lipid levels suggesting that reduced plasma pi plays a role in causing hyperlipidemia in the nephrotic syndrome. To determine whether apolipoprotein (Apo) levels were affected by pi, passive Heymann nephritis (HN) was created in 20 rats. Hyperoncotic (25%) human albumin or ficoll was infused continuously into each of 5 HN rats adjusted to maintain a plasma pi above 20 mm Hg. Either saline or a mixture of amino acids calculated to approximate those released from catabolized human albumin were infused into 5 HN as controls. Urinary rat albumin loss was not different between the 4 groups of HN. Plasma apo A-I, B and E were all increased significantly in saline and amino acid infused HN, but apo A-IV was decreased. Infusion of either albumin or ficoll normalized apo A-I, and apo E levels in HN even though proteinuria continued unabated. In contrast, apo B remained significantly elevated in HN infused with albumin, but was reduced to normal by ficoll. Fifteen non-nephrotic control animals were studied in 3 groups of 5 animals each; one receiving human albumin, one ficoll, both adjusted to increase plasma pi to supranormal levels, and a 3rd group received saline. In contrast to HN, plasma apo A-I, E, and B levels were unaffected by albumin or ficoll infusion in control animals. Ficoll caused a significant reduction in apo A-IV in both HN and control animals to subnormal levels, but albumin infusion was without effect. Reduced plasma pi, but not reduced plasma albumin is necessary for increased apo A-I, and E levels in the nephrotic syndrome. When plasma pi is normal extensive proteinuria does not increase plasma apo A-I or E levels. Factors other than an albumin concentration or pi, such as persistent urinary protein loss, play a role in establishing increased apo B containing lipoproteins in the nephrotic syndrome. Ficoll may cause changes in plasma lipoprotein levels by means other than its ability to increase plasma pi.
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PMID:Effect of plasma oncotic pressure on apolipoprotein levels in rats with Heymann nephritis. 867 21

Type III hyperlipoproteinaemia (HLP) is usually associated with homozygosity for apolipoprotein (apo) E2 (arg-158-->Cys). We identified a 46-year-old white female with severe hyperlipidaemia and the heterozygous apo E3/2* phenotype. Typical clinical characteristics of type III HLP, i.e. palmar xanthomas (orange-yellowish discolorations of the palmar creases) and tuberoeruptive xanthomas, were present in the patient. Without therapy the patient's serum triglycerides (1.098 mg dL(-1)), cholesterol (546 mg dL(-1)), very low-density lipoprotein (VLDL) cholesterol (372 mg dL(-1)) and the apo E concentration (25.0 mg dL(-1)) were distinctly elevated as well as her VLDL cholesterol to serum triglyceride (TG) ratio at 0.34 (normal ratio about 0.2). Direct sequencing of polymerase chain reaction (PCR)-amplified segments of the apo epsilon gene identified a thymine for cytosine (C-->T) exchange in the first base of codon 136 that is predictive for a Cys (TGC) for Arg (CGC) substitution in the encoded amino acid sequence. Two children, an 18-year-old female with the heterozygous apo E4/2* phenotype, a 25-year-old female with the heterozygous apo E3/2* phenotype and the 73-year-old father of the proband with the heterozygous apo E3/2* phenotype are also carriers of the rare mutant. The father has severe atherosclerosis and lipid values compatible with the diagnosis of type III HLP. The affected children have hyper/dyslipidaemia but as yet no clinical expression of the disease. We propose that in the analysed family this rare apo E2 (Arg-136-->Cys) variant is associated with late-onset dominance of type III HLP.
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PMID:Apolipoprotein E2 (Arg-136-->Cys), a variant of apolipoprotein E associated with late-onset dominance of type III hyperlipoproteinaemia. 868 50

Hypertriglyceridemia and hyperlipidemia are common disorders associated with coronary artery disease and premature death. The proteins encoded by the apolipoprotein (apo) A-I/C-III/A-IV gene cluster are involved in the metabolism of both triglycerides and cholesterol. In a large sample of individuals from the ARIC study, six polymorphic markers were typed and plasma lipid values were measured to determine whether the well-established association between the Sst I S2 allele in the 3'-untranslated region of the apo C-III gene and hypertriglyceridemia was due to disequilibrium with variation in the 5' regulatory region of the apo C-III gene. The Sst I polymorphism was significantly associated with hypertriglyceridemia (P = .006) but not with carotid artery wall thickness, plasma apo C-III levels, or elevated cholesterol. The frequency of the S2 allele was 0.14 in those with high triglyceride levels and 0.05 in those with low triglyceride levels. None of the 5' flanking polymorphisms were significantly associated with any of the plasma lipids studied. There was substantial linkage disequilibrium between the Sst I polymorphism and each of the 5' apo C-III polymorphisms; however, the significant association between the apo C-III haplotypes and hypertriglyceridemia (odds ratio, 4.0; P < .0001) was solely attributable to the effects of the Sst I polymorphism (odds ratio, 3.96). As a part of these analyses, we also defined a unique haplotype that is inversely associated with the occurrence of hypertriglyceridemia, suggesting further molecular analyses of this important gene region.
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PMID:Polymorphic markers in apolipoprotein C-III gene flanking regions and hypertriglyceridemia. 869 57

Liver disease is accompanied by major qualitative and quantitative disturbances in plasma lipoprotein metabolism, the extent and intensity of which depend on the degree of parenchymal damage, cholestasis, or both. The main objective of this study was to determine the cholesteryl ester transfer CETP activity and its association with the lipoprotein neutral lipid composition in patients with either liver cirrhosis or cholestasis, as compared to normal controls. Lipoproteins were isolated by ultracentrifugation, lipids and apolipoproteins were measured by conventional methods, and the fatty acid composition was established by gas chromatography; CETP activity in lipoprotein-deficient plasma was measured by determining the transfer of [3H]cholesteryl esters from HDL to VLDL. Lipoprotein lipase and hepatic lipase activities were measured in post-heparin plasma by radiochemical methods. In patients with liver cirrhosis, low levels of VLDL, HDL, apo B, and Lp(a) were observed, as well as a change in the composition of HDL particles, with increases in the relative proportion of triglyceride and free cholesterol. Respectively, the last two changes could be attributed in part to the low hepatic lipase activity observed in this study, and to the low lecithin:cholesterol acyltransferase activity previously observed by others. In patients with cholestasis, a moderate hyperlipidemia due to the elevation of LDL was found. In contrast, HDL and apo A-I levels were very low reflecting a low number of HDL particles, which also had altered compositions with increases in the triglyceride and free cholesterol contents relative to apo A-I and esterified cholesterol, respectively. As regards the fatty acid composition of lipoprotein lipids, the two groups of patients showed, in general, a lower proportion of linoleic acid and a compensating higher proportion of oleic acid as compared to the controls, changes that were observed in both cholesteryl esters and triglycerides. In contrast, the proportions of oleic and palmitoleic acids in phospholipids were increased, whereas that of stearic acid was decreased in patients as compared to controls. In patients with liver cirrhosis, as well as in controls, no changes were observed in the fatty acid compositions of cholesteryl ester, triglycerides, or phospholipids among the different lipoproteins, which probably reflects the equilibration reached by the action of CETP. In patients with cholestasis, no differences were observed in fatty acid composition among the lipoprotein phospholipids but, interestingly, cholesteryl esters from VLDL had a significantly lower linoleic acid content than those from HDL, whereas triglycerides from VLDL had significantly higher oleic acid and lower linoleic acid contents than those from HDL. This distinct fatty acid composition of the neutral lipids between lipoproteins was associated with a significant decrease (25%) in the cholesteryl ester transfer activity in patients with cholestasis. We suggest that fat malabsorption due to the biliary defect may induce a decrease in cholesteryl ester transfer protein synthesis or section, which in turn would slow the equilibration of the neutral lipids among plasma lipoproteins.
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PMID:Cholesteryl ester transfer activity in liver disease and cholestasis, and its relation with fatty acid composition of lipoprotein lipids. 874 May 80

The objective of this study was to determine whether phenolic constituents present in red wine and grape juice modulate plasma lipid and lipoprotein concentrations in healthy human subjects. All subjects consumed in random order 375 ml of red or white wine per day or 500 ml of two different grape juices (high and low phenols) per day for periods of 4 weeks separated by 2-week periods of abstention while continuing normal activity and food intake, and their normal lives in a community setting. The subjects were 24 healthy males aged 26-45 years screened by clinical examination and laboratory tests to exclude hypertension, diabetes mellitus, hyperlipidemia and obesity, among others. Fasting blood was collected at the beginning and end of each beverage schedule for analysis of lipids and lipoproteins. Changes in plasma lipids and lipoproteins in response to each beverage were measured to determine whether these were altered by red wine and grape juice phenolics independently of the effects of ethanol. Both grape juices had virtually no effect. Red and white wines raised plasma HDL-cholesterol and apo A-I and apo A-II concentrations as well as the apo A-I:apo B ratio to a similar extent. Red wine also raised plasma triglyceride and total cholesterol concentrations. Neither wine affected plasma apo B or apo (a) concentrations. The favourable effects of wines in modulating plasma lipid and lipoprotein concentrations are probably due to their alcohol content and cannot be reproduced by grape juices.
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PMID:Wine: does the colour count? 881 66

Ciprofibrate is an effective treatment for three main types of atherogenic hyperlipoproteinaemia: type IIa hypercholesterolaemia, type IIb combined hyperlipidaemia, and type IV hypertriglyceridaemia. In type IIa hypercholesterolaemia, administration of 100 mg/day of ciprofibrate, to approximately 3000 patients, decreased total cholesterol (TC), triglycerides, apolipoprotein B (apo B) and low-density lipoprotein (LDL) cholesterol. Levels of apolipoproteins in high-density lipoprotein (HDL) cholesterol and apolipoprotein AI (apo A-I) were increased. Administration of the same dose of ciprofibrate, to approximately 3500 patients with type IIb combined hyperlipidaemia, had a marked cholesterol- and triglyceride-lowering effect, in addition to producing a decrease in LDL cholesterol and apo B, and an increase in apo A-I. TC levels were also decreased in type IV hypertriglyceridaemia following administration of 100 mg/day of ciprofibrate to 800 patients. The decrease in TC levels was attributable to a decrease in triglyceride levels and an increase in HDL cholesterol levels. The pharmacokinetics, mechanism of action and safety of ciprofibrate treatment are also discussed.
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PMID:Efficacy and safety of ciprofibrate in hyperlipoproteinaemias. 883 20

Vascular access dysfunction is an important cause of morbidity for dialysis patients and a major contributor to hemodialysis cost. Thrombosis is a leading cause of vascular access failure, and usually results from stenotic lesions in the venous outflow system. This study was designed to explore the impact of serum levels of various risk factors for thrombosis and accelerated fibrointimal hyperplasia on progressive stenosis, and the subsequent thrombosis of hemodialysis fistula. A cross-sectional and 2-yr prospective pilot study was performed in 30 nondiabetic hemodialysis patients with primary arteriovenous fistula. Venous dialysis pressure, urea recirculation, color Doppler sonography, and angiography were used to monitor vascular access patency. Eleven patients (37%) developed a progressive stenosis in the venous circuit, which was complicated by thrombosis in three patients. Compared with the patients without fistula dysfunction, these patients had higher serum levels of monocyte chemoattractant protein-1 and interleukin-6, two cytokines that regulate the proliferation of vascular smooth muscle cells, which is the key mechanism in the pathogenesis of fistula stenosis. In addition, they had hyperinsulinemia, hyperlipidemia, and increased plasma levels of two hemostasis-derived risk factors for thrombosis: plasminogen activator inhibitor type 1 and factor VII. Monocyte chemoattractant protein-1, interleukin-6, plasminogen activator inhibitor type 1, factor VII, triglycerides, and the ratios for cholesterol/HDL-cholesterol, apolipoprotein (apo) A-I/ apo C-III, apo A-I/apo B, and glucose/insulin were independent predictors of fistula dysfunction. This study demonstrates the influece of cytokines, hemostasis-derived vascular risk factor, hyperinsullnemia, and abnormallties of lipids and apolipoproteins on primary fistula survival. The assessment of these factors might be useful for the identification of the patients at risk of fistula stenosis and thrombosis.
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PMID:Risk factors for vascular disease and arteriovenous fistula dysfunction in hemodialysis patients. 886 9

The main effect of simvastatin is the decrease of serum cholesterol due to the reduction of LDL. A decrease of serum triglycerides and an increase of HDL-C are commonly observed during the treatment. The reduction of triglycerides is accounted for by the increased catabolism of apo B-containing lipoproteins whereas the mechanisms bringing about the increase of HDL-C are still unknown. We treated 318 patients with primary hyperlipidemia (227 with phenotype IIa and 91 with phenotype IIb) with simvastatin 10 mg a day and after 6 weeks we found a mean 3% increase in HDL-C. HDL-C increased only in about half of the patients and the patients in whom HDL-C increased had baseline higher serum triglycerides and had a greater hypotriglyceridemic response than patients in whom HDL-C did not increase. Accordingly, HDL-C increased in type IIb patients who experienced a greater change in triglycerides than type IIa patients, in whom HDL-C did not increase significantly. Apo A-I levels did not change and apo A-I/HDL-C ratio significantly decreased. At a daily dose of 40 mg, administered to 51 treatment-resistant patients, simvastatin produced a marginally greater decrease in serum cholesterol and LDL-C, but not in serum triglycerides and HDL-C, than at the daily dose of 10 mg. An increase in HDL-C was associated with a reduction in serum triglycerides. The decrease in apo A-I/HDL-C ratio suggests that the increase in HDL-C after simvastatin must be regarded as an enrichment of the cholesterol core of HDL particles. The effect is likely to be due to the decrease of the serum concentration of VLDL bringing about a reduction of cholesterol transfer from apo A-I to apo B-containing lipoproteins.
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PMID:The effect of simvastatin on HDL cholesterol in hyperlipidemic patients. Evidence of a relationship with the changes in serum triglyceride level. 888 Feb 87


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