Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 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

Increased concentration of cholesteryl ester transfer protein (CETP) in plasma favours a lipoprotein profile characterized by a reduced high density lipoprotein (HDL) cholesterol. Previous studies have demonstrated that a diet high in cholesterol and saturated fat (HCSF) is associated with elevated plasma CETP and increased release of cholesterol ester transfer activity (CETA) from hamster adipose tissue incubated in vitro. The present study investigated the effects of vitamin E (Vit.E) ingestion on plasma CETP activity and adipose tissue CETA in Syrian Golden hamsters. A regular diet supplemented by the addition of 1% cholesterol and 10% coconut oil (w/w) was associated with a time-dependent increase in plasma CETP activity and increased release of adipose CETA following incubation of fragments of perirenal adipose tissue. Vit.E ingestion (100 mg/kg body weight per day for 8 weeks) suppressed 85% of the increase of CETA released from cultured hamster adipose tissue and 70% of the increase of plasma CETP activity induced by the HCSF diet. Significant decreases in plasma total and LDL cholesterol and an increase in HDL cholesterol were found in hamsters receiving the HCSF diet plus Vit.E compared to the animals on the HCSF diet alone. In the hamsters on regular chow, Vit.E ingestion alone did not significantly alter adipose tissue CETA, plasma CETP activity or plasma lipoproteins. The results indicate that Vit.E prevents the HCSF diet-induced increase in plasma CETP activity, probably via a reduction of CETA secretion from hamster adipose tissue. This suggests that Vit.E supplementation may help to ameliorate the dyslipidemia caused by a HCSF diet through its inhibitory influence on CETP production in adipose tissue.
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PMID:Effect of dietary vitamin E supplements on cholesteryl ester transfer activity in hamster adipose tissue. 883 Sep 34

The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high-density lipoproteins (HDL) into very-low-density lipoproteins (VLDL) with a reciprocal exchange of triglycerides. Plasma CETP is mainly bound to HDL and is involved in the interconversion of these lipoproteins. In experimental models such as transgenic mice, CETP activity decreases HDL cholesterol and increases the cholesteryl ester content of apo B-containing lipoproteins. In humans, CETP activity and concentration are positively correlated with VLDL-LDL cholesterol. Clinical studies suggest that the effect of CETP on HDL cholesterol depends on the amount of acceptor lipoproteins. CETP activity is negatively correlated with HDL cholesterol only in hypertriglyceridemic states. Various CETP gene mutations have been reported, they induce hyper-alpha-lipoproteinemia. On the other hand, the impact of the variability of CETP gene on HDL cholesterol variations in Caucasians is controversial. CETP is often involved in secondary dyslipidemia and is susceptible to modify the composition of plasma lipoproteins in an atherogenic way. The real impact of CETP activity on atherosclerosis is still unknown. CETP is susceptible to play a proatherogenic role since it mediates a redistribution of plasma cholesterol from lipoproteins associated with a protection against atherosclerosis into the proatherogenic apo B-containing lipoproteins. However, CETP mediates one of the steps of the reverse cholesterol transport, an antiatherogenic process that channels cholesterol from peripheral tissues back to the liver.
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PMID:Cholesteryl ester transfer protein: an enigmatic protein. 896 91

To determine whether enhanced activity of cholesteryl ester transfer protein (CETP) contributes to the development of atherogenic lipoprotein profiles in obese children, plasma CETP activity was assayed according to a micro-method, by co-incubating lipoprotein-deficient samples with exogenous donor and acceptor lipoproteins. The study subjects were 31 obese children (14 males and 17 females). Serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC:high-density lipoprotein (HDL)-C, LDL-C:HDL-C, apolipoprotein (apo) B, and apo B:apo Al were increased in obese children. Thus they appeared to exhibit an atherogenic lipoprotein profile, with a relative decrease in cholesterol carried by HDL compared with the cholesterol in the other lipoprotein fractions. The mean fasting plasma insulin level was also increased. CETP activity was significantly higher in the obese children than in nonobese control children, and was correlated with LDL-C, TC:HDL-C, LDL-C:HDL-C, and apo B:apo Al. These results suggest that an increase in plasma CETP activity results in atherogenic change in lipoprotein metabolism in obese children. The increase in CETP may be due to the adiposity or insulin resistance. Alternatively, dyslipidemia per se, physical inactivity or excessive fat intake, that are commonly found in obese children, may contribute to the increase in CETP activity.
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PMID:Increased plasma cholesteryl ester transfer activity in obese children. 906 17

Insulin resistance is a common metabolic abnormality that is associated with an increased risk of both atherosclerosis and type 2 diabetes. The phenotype of insulin resistance includes a dyslipidemia characterized by an elevation of very low-density lipoprotein triglyceride, a reduction in high-density lipoprotein cholesterol, and the presence of small, triglyceride-enriched low-density lipoproteins. The underlying metabolic abnormality driving this dylipidemia is an increased assembly and secretion of very low-density lipoprotein particles, leading to an increased plasma level of triglyceride. Hypertriglyceridemia, in turn, results in a reduction in the high-density lipoprotein level and the generation of small, dense low-density lipoproteins; these events are mediated by cholesteryl ester transfer protein. In addition, hypertension, obesity, and a prothrombotic state are also integral components of the insulin resistance syndrome. In this review, we will provide a pathophysiologic basis, based on studies on humans and in tissue culture, for the dyslipidemia of insulin resistance. We will also review the effects of insulin resistance on the coagulation and fibrinolytic pathways. It is hoped that this review will allow health professionals better to evaluate and treat their patients with insulin resistance, thereby reducing the very much increased risk of atherosclerotic cardiovascular disease carried by these individuals.
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PMID:The insulin resistance syndrome: impact on lipoprotein metabolism and atherothrombosis. 1114 62

Qualitative and quantitative anomalies of low-density lipoproteins (LDL) play a key role in the pathophysiology of atherosclerosis. Such anomalies are characteristics of the atherogenic dyslipidemias which occur most frequently, i.e. primary hypercholesterolemia of phenotype IIA (including familial hypercholesterolemia), combined hyperlipidemias (Type IIB) and hypertriglyceridemia (Type IV). An elevated concentration of circulating LDL occurs either as a result of hepatic overproduction of VLDL particles, the major precursors of LDL, or as a result of delayed catabolism, as occurs when there is a deficit of cellular LDL receptors (e.g. familial hypercholesterolemia), or as a combination of both. The major qualitative anomaly of LDL which results in elevated atherogenicity involves a predominance of small dense LDL, as seen in patients with premature coronary heart disease and equally in combined hyperlipidemia and in hypertriglyceridemia. The mechanism of the formation of these particles is complex and involves the concerted intravascular action of cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL) and hepatic lipase (HL) on triglyceride-rich precursors of dense LDL Lipid-lowering agents, such as fibrates and statins, act to reduce the atherogenicity of dense LDL by distinct mechanisms, which lead to normalisation of circulating LDL levels and/or to targeted reduction in dense particles of elevated atherogenicity. Indeed, such pharmacological probes have facilitated new insight into the molecular and cellular mechanisms which underlie each of the major forms of atherogenic dyslipidemia.
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PMID:[Role of anomalies of low density lipoproteins (LDL) in atherogenicity]. 1147 67

Cholesteryl ester transfer protein (CETP) plays a pivotal role in the reverse transport of cholesterol and in the remodeling of circulating lipoproteins. While plasma and adipose tissue levels of CETP are affected by a variety of metabolic conditions, the extent of the effects of dietary factors, other than high cholesterol feeding, are not well understood. To further explore this paradigm, male Golden Syrian hamsters were fed for 4 weeks with a 60%-enriched fructose diet (F) and were compared to a matched group of animals fed with a normal chow diet (N). After feeding for 4 weeks, plasma insulin concentrations were lower in animals fed fructose than in control animals (F: 3.3+/-0.8 vs N: 7.4+/-1.9 ng/mL; p<0.03), but there was no significant difference in plasma glucose concentrations between the two groups (F: 138+/-7 vs N: 148+/-10 mg/dL; p>0.05). Fructose-fed animals showed significant increases in plasma triglyceride (F: 269+/-22 vs N: 165+/-22 mg/dL; p<0.01) and plasma cholesterol (F: 150+/-10 vs N: 113+/-6 mg/dL; p<0.02) concentrations compared with control animals. Total CETP activity and immunoreactive mass were higher in the plasma of fructose-fed animals that in that of controls (F: 1036+/-70 vs N: 826+/-43 pmol/h/mL, p<0.04 and F: 24.5+/-3.1 vs N: 37.5+/-4.3 AU, p<0.02, respectively). Adipose tissue CETP mRNA levels, assessed by the very sensitive ribonuclease protection assay, were 53% higher in fructose-fed animals than in controls (F: 14.1+/-2.0 vs N: 9.2+/-1.0 AU over a rRNA control; p<0.04). Adipose tissue CETP activity and immunoreactive mass also showed a statistically significant increase in the fructose-fed hamsters compared with those fed a normal diet (p<0.04). In conclusion, fructose feeding in Syrian hamsters induces a mixed dyslipidemia. These metabolic changes are accompanied by a significant increase in CETP levels, both in plasma and in adipose tissue. This phenomenon suggests that the increase in the expression of adipose tissue CETP may be caused either by the ambient hypercholesterolemia resulting from fructose feeding or by an attenuation of a possible inhibitory effect of plasma insulin concentrations on the expression of adipose tissue CETP in this feeding paradigm.
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PMID:Induction of cholesteryl ester transfer protein in adipose tissue and plasma of the fructose-fed hamster. 1147 89

Hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) have been independently associated with low density lipoprotein (LDL) and high density lipoprotein (HDL) size in different cohorts. These studies have been conducted mainly in men and in subjects with dyslipidemia. Ours is a comprehensive study of the proposed biochemical determinants (lipoprotein lipase, HL, CETP, and triglycerides) and genetic determinants (HL gene [LIPC] and Taq1B) of small dense LDL (sdLDL) and HDL subspecies in a large cohort of 120 normolipidemic, nondiabetic, premenopausal women. HL (P<0.001) and lipoprotein lipase activities (P=0.006) were independently associated with LDL buoyancy, whereas CETP (P=0.76) and triglycerides (P=0.06) were not. The women with more sdLDL had higher HL activity (P=0.007), lower HDL2 cholesterol (P<0.001), and lower frequency of the HL (LIPC) T allele (P=0.034) than did the women with buoyant LDL. The LIPC variant was associated with HL activity (P<0.001), HDL2 cholesterol (P=0.034), and LDL buoyancy (P=0.03), whereas the Taq1B polymorphism in the CETP gene was associated with CETP mass (P=0.002) and HDL3 cholesterol (P=0.039). These results suggest that HL activity and HL gene promoter polymorphism play a significant role in determining LDL and HDL heterogeneity in healthy women without hypertriglyceridemia. Thus, HL is an important determinant of sdLDL and HDL2 cholesterol in normal physiological states as well as in the pathogenesis of various disease processes.
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PMID:Contribution of hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein to LDL and HDL heterogeneity in healthy women. 1195 Jul 8

Hemodialysis (HD) patients have a high mortality rate due to vascular disease (VD). Therefore, we investigated the effect of uremic dyslipidemia on VD in HD patients, with special consideration of the reverse cholesterol transport (RCT) system including high-density-lipoprotein cholesterol (HDL-C), cholesteryl ester transfer protein (CETP) and its genetic (D442G) mutation. In 414 HD patients, a sub-median HDL-C level (< 48 mg/dl) was an independent risk factor for VD. In the lower HDL-C status, the CETP mutation leading to CETP levels was independently associated with VD. In 210 selected patients, the CETP level was an independent protective factor against VD among those with higher HDL-C levels (> 45 mg/dl). We also measured serum homocysteine (Hcy) levels and examined its association with VD considering that hyperhomocysteinemia is a newly identified risk factor for atheroma. HD Patients (n = 545) had about 3 times the Hcy levels of the general population. A common C677T mutation in the gene of methylenetetrahydrofolate reductase (MTHFR) involved in Hcy metabolism was independently and directly related to serum Hcy levels with TT genotype patients having the highest levels. Patients with the TT genotype were younger and had a shorter duration of dialysis than those with the CT or CC genotype after adjustment for age at the initiation of dialysis, although there was no difference in VD prevalence among the genotypes and no association between Hcy levels and VD prevalence. In conclusion, lower HDL-C and CETP status was a risk factor for VD in HD patients, suggesting the importance of RCT. Serum Hcy levels were markedly increased in HD patients and the TT genotype may be associated with higher mortality. However, a large-scale prospective study is required to clarify whether hyperhomocysteinemia or the TT genotype is a VD risk factor among HD patients.
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PMID:[Risk factors for atherosclerotic vascular disease in patients on maintenance hemodialysis--with especial respect to reverse cholesterol transport system and hyperhomocysteinemia]. 1237 16

Cholesteryl ester transfer protein (CETP) is a key factor in plasma reverse cholesterol transport and is implicated in the pathophysiology of atherogenic dyslipidemia. Variations observed in plasma CETP mass and activity in both normolipidemic and dyslipidemic individuals may reflect differences in CETP gene expression. We evaluated the respective roles of the Sp1 and Sp3 transcription factors on the promoter activity of the human CETP gene at a new Sp1/Sp3 site identified at position -690, and at two previously described Sp1/Sp3 sites at positions -37 and -629. In transient transfection in HepG2 cells, site-directed mutagenesis using luciferase reporter constructs containing a promoter fragment from +32 to -745 indicated that the new -690 site acts as a repressive element in reducing CETP promoter activity (-22%; P < 0.05); equally, this site exerts an additive effect with the -629 site, inducing marked repression (-42%; P < 0.005). In contrast, in NCTC cells that display a 16-fold lower level of Sp3, the repressive effect at the -690 site was enhanced 2-fold (-45%; P < 0.05), whereas the -629 site exerted no effect. Cotransfection of Sp1 and/or Sp3 in SL2 insect cells lacking endogenous Sp factors demonstrated that Sp1 and Sp3 act as activators at the -690 and -37 sites, whereas Sp3 acts as a repressor at the -629 site. Taken together, our data demonstrate that Sp1 and Sp3 regulate human CETP promoter activity through three Sp1/Sp3 binding sites in a distinct manner, and that the Sp1/Sp3 ratio is a key factor in determining the relative contribution of these sites to total promoter activity.
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PMID:Regulation of human CETP gene expression: role of SP1 and SP3 transcription factors at promoter sites -690, -629, and -37. 1273 Mar 2


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