UMLS:C0020473 - FACTA Search

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Query: UMLS:C0020473 (hyperlipidemia)
15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperlipidemia is a prominent feature of the nephrotic syndrome. Lipoprotein abnormalities include increased very low and low density lipoprotein (VLDL and LDL) cholesterol and variable reductions in high density lipoprotein (HDL) cholesterol. We hypothesized that plasma cholesteryl ester transfer protein (CETP), which influences the distribution of cholesteryl esters among the lipoproteins, might contribute to lipoprotein abnormalities in nephrotic syndrome. Plasma CETP, apolipoprotein and lipoprotein concentrations were measured in 14 consecutive untreated and 7 treated nephrotic patients, 5 patients with primary hypertriglyceridemia, and 18 normolipidemic controls. Patients with nephrotic syndrome displayed increased plasma concentrations of apoB, VLDL, and LDL cholesterol. The VLDL was enriched with cholesteryl ester (CE), shown by a CE/triglyceride (TG) ratio approximately twice that in normolipidemic or hypertriglyceridemic controls (P < 0.001). Plasma CETP concentration was increased in patients with untreated nephrotic syndrome compared to controls (3.6 vs. 2.3 mg/l, P < 0.001), and was positively correlated with the CE concentration in VLDL (r = 0.69, P = 0.004) and with plasma apoB concentration (r = 0.68, P = 0.007). Treatment with corticosteroids resulted in normalization of plasma CETP and of the CE/TG ratio in VLDL. An inverse correlation between plasma CETP and HDL cholesterol was observed in hypertriglyceridemic nephrotic syndrome patients (r = -0.67, P = 0.03). The dyslipidemia of nephrotic syndrome includes increased levels of apoB-lipoproteins and VLDL that are unusually enriched in CE and likely to be atherogenic. Increased plasma CETP probably plays a significant role in the enrichment of VLDL with CE, and may also contribute to increased concentrations of apoB-lipoproteins and decreased HDL cholesterol in some patients.
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PMID:Increased concentration of plasma cholesteryl ester transfer protein in nephrotic syndrome: role in dyslipidemia. 147 91

Cholesteryl ester transfer from solid-phase bound HDL to endogenous plasma HDL or VLDL/LDL was determined in 50 patients with primary disorders of lipid metabolism and 27 normolipidemic subjects. Transfer to the plasma HDL pool was significantly reduced in familial hypercholesterolemia, familial combined hyperlipidemia, hypoalphalipoproteinemia and dysbetalipoproteinemia. Subfractionation of HDL revealed that the lipid transfer to HDL3 was significantly reduced in all patient groups while transfer to HDL2 was increased in those with dysbetalipoproteinemia and familial hypertriglyceridemia. Transfer to LDL and VLDL was increased only in patients with dysbetalipoproteinemia and hypoalphalipoproteinemia. Reduced transfer to HDL occurred in samples with altered HDL composition; particularly where HDL-triglyceride was significantly increased and HDL-cholesteryl esters were reduced. Transfer of cholesteryl ester to HDL3 was significantly decreased in patients with vascular disease. These findings indicate that impaired interaction of cholesteryl ester transfer protein with the HDL3 pool may contribute to the risk of coronary heart disease in patients with specific plasma lipid abnormalities.
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PMID:Relationship between cholesteryl ester transfer activity and high density lipoprotein composition in hyperlipidemic patients. 275 50

Alimentary lipemia stimulates the transfer of cholesteryl ester between lipoproteins in vitro and may alter lipoprotein cholesteryl ester distribution in vivo. The effect of a single, large oral fat load on lipoprotein cholesteryl ester redistribution and the activity of cholesteryl ester transfer protein was investigated in six normolipidemic men (Group A), six combined hyperlipidemic men (Group B), and six hypercholesterolemic men (Group C). Fasting triglyceride-rich lipoprotein cholesteryl ester was high in Group B, low in Group A, and intermediate in Group C (A less than C less than B, p less than 0.05). After an oral fat load, total plasma cholesteryl ester was unchanged in all groups. In Group A, cholesteryl ester increased in smaller triglyceride-rich lipoproteins and remained so at 24 hours. Conversely, low density and high density lipoprotein cholesteryl ester decreased and returned to fasting values at 24 hours. In Group B, cholesteryl ester increased in large triglyceride-rich lipoproteins. Low density and high density lipoprotein cholesteryl ester (expressed as percentage of plasma cholesteryl ester) decreased. By contrast, in Group C, triglyceride-rich lipoprotein and low density lipoprotein cholesteryl ester remained unaltered, and only high density lipoprotein cholesteryl ester decreased. The activity of cholesteryl ester transfer protein increased in all groups and returned to fasting values at 24 hours. No differences in response were observed among the three groups. It is concluded that an oral fat load can induce a shift in lipoprotein cholesteryl ester distribution from high and low density lipoproteins to triglyceride-rich lipoproteins without affecting total plasma cholesteryl ester.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alimentary lipemia-induced redistribution of cholesteryl ester between lipoproteins. Studies in normolipidemic, combined hyperlipidemic, and hypercholesterolemic men. 278 75

In vitro lipoprotein lipase enhances the cholesteryl ester transfer protein (CETP)-mediated transfer of cholesteryl esters from high density lipoproteins (HDL) to very low density lipoproteins as a result of lipolysis-induced alterations in lipoprotein lipids that lead to increased binding of CETP. To determine if there are similar changes during alimentary lipemia, we measured the transfer of cholesteryl esters from HDL to apo B-containing lipoproteins in incubated fasting and postprandial plasma. In seven normolipidemic subjects there was 2-3-fold stimulation of cholesteryl ester transfer in alimentary lipemic plasma. Cholesteryl ester transfer was stimulated when either the d less than 1.063-or d greater than 1.063-g/ml fraction of lipemic plasma was recombined with its complementary fraction of fasting plasma. To determine the distribution of CETP, plasma was fractionated by agarose chromatography and CETP activity was measured in column fractions in a standardized assay. In fasting plasma, most of the CETP was in smaller HDL, and a variable fraction was nonlipoprotein bound. During lipemia there was increased binding of CETP to larger phospholipid-enriched HDL and in two subjects an increase in CETP in apo B-containing lipoproteins. The total CETP activity of fractions of lipemic plasma was increased 1.1-1.7-fold compared with fasting plasma. Lipemic CETP activity was also increased when measured in lipoprotein-free fractions after dissociation of CETP from the lipoproteins. When purified CETP was incubated with phospholipid-enriched HDL isolated from alimentary lipemic or phospholipid vesicle-treated plasma, there was increased binding of CETP to the phospholipid-enriched HDL compared with fasting HDL, with a parallel stimulation in CETP activity. Thus, the pronounced stimulation of cholesteryl ester transfer during alimentary lipemia is due to (a) an increased mass of triglyceride-rich acceptor lipoproteins, (b) a redistribution of CETP, especially increased binding to larger phospholipid-enriched HDL, and (c) an increase in total activity of CETP, perhaps due to an increased CETP mass.
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PMID:Mechanisms of enhanced cholesteryl ester transfer from high density lipoproteins to apolipoprotein B-containing lipoproteins during alimentary lipemia. 395 85

The transfer of cholesteryl esters and apolipoprotein E has been studied between plasma HDL and chylomicrons isolated either from ascitic fluid or from the plasma of a patient with type V hyperlipoproteinemia. Whereas apolipoprotein E transfer was rapid and occurred at low temperature, cholesteryl ester transfer was suppressed at 4 degrees C. Apolipoprotein E transfer did not depend upon the presence of cholesteryl ester transfer protein and was in fact inhibited by the partially purified preparation of this protein. Apolipoprotein E transfer was not increased by reduction with dithiothreitol. The transfer of cholesteryl esters increased sharply at a chylomicron to HDL ratio of cholesteryl ester above 1/10, a value which may be of physiological significance at the peak of postprandial lipemia. At this ratio, the transfer of apolipoprotein E was minimal and increased only at ratios above 2/1. From these results, it is concluded that there is no connection between apolipoprotein E and cholesteryl ester transfer from HDL to chylomicrons. It is, therefore, proposed that whereas chylomicron apolipoprotein E is acquired rapidly and mostly in the lymphatic system, the concentration of chylomicron cholesteryl esters increases significantly and independently in the circulation.
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PMID:Cholesteryl ester and apolipoprotein E transfer between human high density lipoproteins and chylomicrons. 686 Jun 92

Despite the definite etiologic link between apolipoprotein (apo) E mutations and type III hyperlipoproteinemia (HLP), it is not clear what additional factors are involved in the development of florid hyperlipidemia and how to explain the wide variability in the expression of the hyperlipidemic phenotype in carriers of receptor binding-defective apoE variants. The present study was designed to determine whether the overexpression of cholesteryl ester transfer protein (CETP), a plasma protein that transfers cholesteryl esters from the high density lipoproteins (HDL) to the very low density lipoproteins (VLDL) and whose activity is increased in hyperlipidemic states, plays a role in the development of hyperlipidemia and beta-VLDL accumulation in type III HLP. We produced double-transgenic mice that co-expressed high levels of simian CETP and either high or low levels of a human receptor binding-defective apoE variant, apoE(Cys-142). We previously reported that apoE(Cys-142) high-expresser mice showed spontaneous hyperlipidemia and accumulation of beta-VLDL, whereas the low-expresser mice showed only a modest increase in VLDL cholesterol. Co-expression of CETP induced a massive transfer of cholesteryl esters from the HDL to the VLDL in both lines of double-transgenic mice. As a result, HDL cholesterol and apoA-I levels were reduced to about 50% of normal, VLDL cholesterol increased 2.5-fold, and the cholesteryl ester content of VLDL reached values similar to those observed in human beta-VLDL. The ratio of defective to normal apoE in VLDL was unaffected by CETP co-expression and was higher in animals expressing high apoE levels. Finally, in spite of an increased accumulation of beta-VLDL in the high-expresser mice, the VLDL of the low-expresser mice maintained pre-beta mobility upon co-expression of CETP. The results of this study demonstrate that the ratio of defective to normal apoE on the VLDL, rather than the cholesteryl ester content of VLDL, is the major factor determining the development of severe hyperlipidemia and the formation and accumulation of beta-VLDL in type III HLP.
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PMID:Co-expression of cholesteryl ester transfer protein and defective apolipoprotein E in transgenic mice alters plasma cholesterol distribution. Implications for the pathogenesis of type III hyperlipoproteinemia. 779 36

In 11 patients with IIB hyperlipoproteinemia we studied fasting lipids, lipoproteins, lipoprotein-modifying enzymes, and postprandial lipid metabolism after a standardized oral fat load supplemented with vitamin A before and 12 weeks after treatment with fenofibrate, a third-generation fibric acid derivative. Fasting plasma cholesterol, triglycerides, low-density lipoprotein cholesterol decreased significantly (P < 0.05, P < 0.01, P < 0.01), high-density lipoprotein subfraction 3 cholesterol increased significantly (P < 0.05), and high-density lipoprotein subfraction 2 cholesterol remained unchanged. Postprandial lipemia, i.e., the integrated postprandial triglyceride concentrations corrected for the fasting triglyceride level, and postprandial chylomicron concentrations, as assessed by biosynthetic labeling of chylomicrons with retinyl palmitate, decreased by 40.6% and 60.1% (P < 0.05; P < 0.05), respectively. The activity of lipoprotein lipase (LPL) increased by 33.6% (P < 0.05); the increase in LPL during fenofibrate treatment was positively correlated with the increase in high-density lipoprotein cholesterol (r = 0.84; P < 0.005). Hepatic lipase and cholesteryl ester transfer protein mass and activity remained unchanged. We conclude that lipid-lowering therapy with fenofibrate ameliorates fasting and, more profoundly, postprandial lipoprotein transport in hypertriglyceridemia by curbing postprandial triglyceride and chylomicron accumulation, at least in part, through an increase in LPL activity.
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PMID:Fenofibrate improves postprandial chylomicron clearance in II B hyperlipoproteinemia. 804 77

Two subpopulations of apolipoprotein A-I-containing lipoproteins, those containing only apoA-I (LpA-I) and those containing both apoA-I and apoA-II (LpA-I/A-II), were isolated by immunoaffinity chromatography of plasma from 44 subjects, comprising four groups (male or female, with or without hyperlipidemia). ApoA-I-defined particles (LpAs) were assessed for their content of cholesteryl ester transfer protein (CETP) and for their ability to act as substrates for CETP. Although plasma CETP concentration was similar in all groups, the plasma concentration of LpA-I-associated CETP was significantly higher in females than in males (1.56 +/- 0.11 versus 0.93 +/- 0.13 mg/l, P < 0.05). In females, the major fraction of CETP was found in LpA-I, whereas in normolipidemic males CETP was evenly distributed between LpA-I and LpA-I/A-II, and in hyperlipidemic males the majority of CETP was found in LpA-I/A-II. In all groups, the percentage of CETP in LpA-I was correlated with the concentration of apoA-I in LpA-I (r = 0.64, P < 0.001). Native gradient gel electrophoresis of isolated LpAs showed that CETP was broadly distributed within different sized particles. LpA-I and LpA-I/A-II showed similar efficiency of CETP-mediated cholesteryl ester exchange with LDL. In conclusion, even though LpA-I has a much higher apparent affinity for CETP than LpA-I/A-II, both LpAs can bind CETP and act as equivalent CETP substrates in vitro. Thus, in subjects with low levels of LpA-I (notably hyperlipidemic males), most of the plasma neutral lipid exchange will involve LpA-I/A-II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gender effects on the distribution of the cholesteryl ester transfer protein in apolipoprotein A-I-defined lipoprotein subpopulations. 807 2

To gain insight into metabolic determinants of high density lipoproteins (HDL) containing apolipoproteins A-I and A-II (LpA-I/A-II) and those containing A-I, but devoid of A-II (LpA-I), the plasma concentration of LpA-I and LpA-I/A-II within the HDL2 and HDL3 density spectrum was measured in 14 normolipidemic male subjects on a standardized diet. Apolipoprotein plasma concentrations of HDL subspecies were compared with the magnitude of postprandial lipemia, activities of lipoprotein lipase and hepatic lipase in postheparin plasma, plasma lecithin:cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) mass. Plasma levels of LpA-I/A-II were 2.5 times higher than levels of LpA-I (123 +/- 20 vs. 48.3 +/- 22.1 mg protein/dl) and the partition of LpA-I and LpA-I/A-II between HDL2 and HDL3 differed in that the proportion of LpA-I associated with HDL2 was greater than that of LpA-I/A-II (23 +/- 19 vs. 6 +/- 6%, P < 0.002). With increasing levels of HDL2, the proportion of LpA-I in HDL2 increased (P < 0.002). Furthermore, levels of LpA-I and LpA-I/A-II were strongly correlated within the HDL2 but not within the HDL3 density region. Plasma levels of LpA-I, but not LpA-I/A-II, were inversely correlated with the magnitude of postprandial lipemia. However, activities of lipoprotein lipase and hepatic lipase tended to show stronger associations with the partition of LpA-I/A-II between HDL2 and HDL3 than with that of LpA-I. Within the HDL3, but not the HDL2 density spectrum, LpA-I/A-II exhibited a positive association with plasma LCAT activity, while LpA-I displayed an inverse association with plasma CETP mass. These results are consistent with differences in substrate properties of LpA-I and LpA-I/A-II for lipoprotein modifying enzymes and imply different, but overlapping metabolic pathways of LpA-I and LpA-I/A-II.
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PMID:High density lipoproteins with differing apolipoproteins: relationships to postprandial lipemia, cholesteryl ester transfer protein, and activities of lipoprotein lipase, hepatic lipase, and lecithin: cholesterol acyltransferase. 816 33

Hyperlipidemia is one of the risk factors for coronary atherosclerosis and the establishment of its simple etiological diagnosis is crucial. Hyperlipidemia can be classified into primary and secondary hyperlipidemia. Primary hyperlipidemia includes familial lipoprotein lipase (LPL) deficiency, familial hypercholesterolemia (FH), familial type III hyperlipidemia, and familial combined hyperlipidemia. Many genetic mutations have been identified in patients with familial LPL deficiency and FH. An ELISA kit has been established to determine LPL mass levels, using monoclonal antibodies against LPL. FH is a deficiency of LDL receptor and is characterized by marked hypercholesterolemia and Achilles tendon xanthomas. It can be diagnosed by an LDL receptor assay, using 125I-LDL in skin fibroblasts. However, the diagnosis can be made easily by measuring the uptake of DiI-LDL by peripheral lymphocytes. Familial type III hyperlipidemia is a genetic disorder characterized by the presence of a broad beta pattern in lipoprotein electrophoresis and is based upon the abnormality of apo E isoform (apo E2/2). Apo E4 has been shown to be associated with late-onset Alzheimer's disease. Cholesteryl ester transfer protein (CETP) deficiency is characterized by a marked hyperalphalipoproteinemia and various abnormalities in the size and composition of LDL and HDL. Two common mutations in the CETP deficiency have been identified; an intron 14 splicing defect and D442: G missense mutation. These mutations account for at least one half of hyper-HDL-cholesterolemia in the Japanese. We have recently identified an area (Omagari City, Akita) where the frequency of heterozygotes for the intron 14 splicing defect is approximately 28% of the general population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Progress in the diagnosis of endocrine and metabolic disorders: hyperlipidemia]. 855 75

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