Accelerated transfer of cholesteryl esters in dyslipidemic plasma. Role of cholesteryl ester transfer protein.

Tall, Alan R.; Granot, Esther; Brocia, R W; Tabas, Ira; Hesler, C B; Williams, Kieran R.; Denke, Margo A.

doi:10.1172/jci112940

Cited by 185 publications

(81 citation statements)

References 35 publications

(22 reference statements)

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“…Previous studies also demonstrated that CETP activity in lipoprotein-free plasma was increased in dysbetalipoproteinemia. 16 In the present study, for both chylomicronemic and dysbetalipoproteinemic subjects, correction of the phenotypic profile by dietary means resulted in normalization of the CETP concentration, suggesting that the observed increases in plasma concentrations of CETP were, at least in part, secondary to the lipoprotein abnormality.…”

Section: Discussionsupporting

confidence: 54%

“…16 Briefly, plasma (<6 nmol HDL cholesterol) was mixed with tritium-labeled CE-containing HDL3 (24 nmol CE) and an excess of acceptor LDL (500 nmol CE) in a final volume of 100 /xl 50 mM tris(hydroxymethyl)aminomethane, 150 mM NaCl, 2 mM EDTA buffer, pH 7.4. Samples and blanks containing no plasma were incubated for 3 hours at 37°C.…”

Section: Cholesteryl Ester Transfer Activity Assaymentioning

confidence: 99%

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Plasma concentrations of cholesteryl ester transfer protein in hyperlipoproteinemia. Relation to cholesteryl ester transfer protein activity and other lipoprotein variables.

McPherson

Mann

Tall

et al. 1991

Arterioscler Thromb

198

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Cholesteryl ester transfer protein (CETP) mediates an important pathway for reverse cholesterol transport. Concentrations of CETP in fasting plasma were measured by radioimmunoassay in two different groups of hyperlipoproteinemic subjects. Plasma CETP concentrations measured by radioimmunoassay correlated closely with cholesterol ester transfer activity in normal plasma (r=0.86). In the first group of 58 patients, plasma CETP concentrations were significantly increased, as compared with those in 79 normal subjects and in hypercholesterolemic (+26%) and combined hyperlipoproteinemic (+25%) subjects but were not altered in moderately hypertriglyceridemic subjects. Marked elevations in plasma CETP levels were documented in patients with dysbetalipoproteinemia (+68%) and severe chylomicronemia (+85%). Similar results were obtained in a second population of 50 hyperlipoproteinemic subjects. Significant correlations were found between plasma CETP levels and total cholesterol (r=0.52), very low density lipoprotein (VLDL) cholesterol (r=0.63), and apolipoprotein E concentration (r=0.40). Correction of the lipoprotein phenotype by dietary means resulted in significant reductions in plasma CETP concentrations in patients with chylomicronemia and dysbetalipoproteinemia. In these subjects, plasma high density lipoprotein cholesterol concentrations increased as CETP decreased. These studies indicate that CETP levels increase in association with enhanced peripheral cholesterol transport via low density lipoprotein, /3-VLDL, or chylomicron remnants. (Arteriosclerosis and Thrombosis 1991;ll:797-804) E arly studies by Rehnborg and Nichols 1 and Nichols and Smith 2 demonstrated that on incubation of normolipemic plasma, cholesteryl ester (CE) increased in very low density lipoprotein (VLDL), whereas triglyceride (TG) concentration decreased in VLDL but increased in high density lipoprotein (HDL) and low density lipoprotein (LDL). These experiments were the first to document CE transfer between lipoproteins, a phenomenon that was further clarified by the demonstra- tion by Zilversmit et al 3 that the d>1.21 g/ml fraction contained a protein that catalyzed CE transfer between lipoproteins, a protein that is now identified as cholesteryl ester transfer protein (CETP). More recently, two research groups have purified and characterized CETP, which is a very hydrophobic protein with a molecular size of M r 74,000, 45 in agreement with the data derived from the cloning and sequencing of the cDNA encoding for CETP. 6 While CETP mediates only the exchange of CEs between HDL and LDL, 7 it does promote net transfer of CEs from HDL to VLDL and chylomicrons. 8 This specificity of the transfer reaction makes it a major pathway for reverse cholesterol transport in many mammalian species. However, the significance of plasma levels of CETP in atherosclerosis must be considered in terms of the two facets of the CETPmediated system -factors facilitating the accumulation of HDL CE (secretion of nascent HDL, its interaction with peripheral cells...

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Section: Discussionsupporting

confidence: 54%

Section: Cholesteryl Ester Transfer Activity Assaymentioning

confidence: 99%

Plasma concentrations of cholesteryl ester transfer protein in hyperlipoproteinemia. Relation to cholesteryl ester transfer protein activity and other lipoprotein variables.

McPherson

Mann

Tall

et al. 1991

Arterioscler Thromb

198

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“…3 H]cholesteryl ester-labeled HDL (Amersham), and was based on minor modifications of the transfer assay described by Tall et al 25 The percentage transfer of [ 3 H]cholesteryl ester to the LDL acceptor was determined by heparin-manganese chloride precipitation of the LDL fraction and quantitation of counts remaining with the HDL supernatant.…”

Section: Cholesteryl Ester Transfer Protein Assaymentioning

confidence: 99%

Estrogen-Mediated Increases in LDL Cholesterol and Foam Cell–Containing Lesions in Human ApoB100×CETP Transgenic Mice

Zuckerman

Evans

Schelm

et al. 1999

ATVB

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Abstract-The murine double transgenic mouse expressing both human apoB100 and cholesteryl ester transfer protein (CETP), has been used as a model to understand the effects mediated by various therapeutic modalities on serum lipoproteins and on atherosclerotic lesion progression. In the present study the effects of estrogen therapy on serum lipoproteins were investigated after mice were placed on an atherosclerotic diet. The daily oral administration of 20 or 100 g/kg of 17 ␣-ethinyl estradiol resulted in a significant, dose-dependent increase in LDL cholesterol over a 20-week regimen. These differences were apparent by 6 weeks and further increases were observed through the 20-week period. Although CETP did result in a reduction in total HDL, estrogen did not have any impact on the amount of CETP activity associated with the HDL particles. The significant increase in LDL cholesterol was associated with increases in the amount of apoB100 and B48 and apoE-containing particles. Hepatic apoB message levels, however, were not different between the experimental groups. Although the extent of atherosclerotic lesions was modest, Ͻ0.5% of the aortic surface area in the vehicle group, the high-dose estrogen group, showed an increase in lesion area consistent with the elevation in LDL cholesterol. These lesions, primarily restricted to the aortic root and aortic semilunar valves, were more intensely stained with Oil Red O in the high-dose estrogen group when compared with the vehicle controls. (Arterioscler Thromb

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“…However, LTIP levels are elevated in hypercholesterolemia (8). In comparison, CETP levels are increased in hypercholesterolemic subjects and typically unchanged in hypertriglyceridemic subjects (9)(10)(11). In cholesterol-fed animals, increased plasma CETP levels are accompanied by marked increases in hepatic and extrahepatic CETP mRNA (12)(13)(14)(15), but it is not known how cholesterol feeding affects plasma levels of LTIP or LTIP gene expression.…”

mentioning

confidence: 99%

Molecular cloning of hamster lipid transfer inhibitor protein (apolipoprotein F) and regulation of its expression by hyperlipidemia

Izem

Morton

2009

Journal of Lipid Research

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Lipid transfer inhibitor protein (LTIP) is a regulator of cholesteryl ester transfer protein (CETP) function. Factors affecting plasma LTIP levels are poorly understood. In humans, plasma LTIP is elevated in hypercholesterolemia. To define possible mechanisms by which hyperlipidemia modifies LTIP, we investigated the effects of hypercholesterolemic diets on plasma LTIP and mRNA levels in experimental animals. The hamster, which naturally expresses CETP, was shown to express LTIP. Hamster LTIP mRNA, exclusively detected in the liver, defined a predicted LTIP protein that is 69% homologous to human, with an isoelectric point of 4.15 and Mr 5 ?16.4 kDa. Hyperlipidemia induced by feeding hydrogenated coconut oil, cholesterol, or both lipids increased plasma LTIP mass up to 2.5-fold, with LTIP mass correlating strongly with plasma cholesterol levels. CETP mass was similarly affected by these diets. In contrast, these diets reduced LTIP hepatic mRNA levels by .50%, whereas CETP mRNA was increased. Similar results for both CETP and LTIP were also observed in cholesterolfed rabbits. In conclusion, we report in hamster and rabbit that dietary lipids regulate LTIP. Diet-induced hypercholesterolemia markedly increased plasma LTIP mass while concomitantly depressing LTIP gene expression. CETP and LTIP have distinct responses to dietary lipids.-Izem, L., and R. E. Morton. Molecular cloning of hamster lipid transfer inhibitor protein (apolipoprotein F) and regulation of its expression by hyperlipidemia. J. Lipid Res. 2009. 50: 676-684. Supplementary key words rabbit • cholesterol • hydrogenated coconut oil Cholesteryl ester transfer protein (CETP) is an important regulator of lipoprotein composition, and its activity affects plasma lipoprotein levels (1-3). Lipid transfer inhibitor protein (LTIP), also known as apolipoprotein F (apoF), impacts CETP activity in a unique way compared with other factors that have been proposed to regulate CETP activity. Unlike general inhibitors of CETP activity, LTIP tailors CETP-mediated transfer events, inhibiting some and promoting others (4, 5). We have proposed that the balance of CETP and LTIP activities is important in defining the flux of CETP substrates, cholesteryl ester, and triglyceride, between lipoproteins (5-7).Factors affecting plasma levels of LTIP are poorly understood. In several human studies, LTIP levels were shown to correlate negatively with triglyceride levels (6, 8), although this correlation appears to occur only in males (6). However, LTIP levels are elevated in hypercholesterolemia (8). In comparison, CETP levels are increased in hypercholesterolemic subjects and typically unchanged in hypertriglyceridemic subjects (9-11). In cholesterol-fed animals, increased plasma CETP levels are accompanied by marked increases in hepatic and extrahepatic CETP mRNA (12-15), but it is not known how cholesterol feeding affects plasma levels of LTIP or LTIP gene expression.To understand the changes in plasma LTIP that are observed in various hyperlipidemic patient populat...

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Accelerated transfer of cholesteryl esters in dyslipidemic plasma. Role of cholesteryl ester transfer protein.

Cited by 185 publications

References 35 publications

Plasma concentrations of cholesteryl ester transfer protein in hyperlipoproteinemia. Relation to cholesteryl ester transfer protein activity and other lipoprotein variables.

Plasma concentrations of cholesteryl ester transfer protein in hyperlipoproteinemia. Relation to cholesteryl ester transfer protein activity and other lipoprotein variables.

Estrogen-Mediated Increases in LDL Cholesterol and Foam Cell–Containing Lesions in Human ApoB100×CETP Transgenic Mice

Molecular cloning of hamster lipid transfer inhibitor protein (apolipoprotein F) and regulation of its expression by hyperlipidemia

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