Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects.

Lagrost, Laurent; Gandjini, Hassan; Athias, Anne; Guyard-Dangremont, Valérie; Lallemant, Christian; Gambert, Philippe

doi:10.1161/01.atv.13.6.815

Cited by 115 publications

(62 citation statements)

References 59 publications

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“…30 Recent studies have demonstrated the role of CETP activity on the size redistribution of LDL and HDL profiles in normolipidemic subjects. 31 These data suggest that lipid exchange between HDL and the apoB-containing lipoproteins mediated by CETP could actively modulate the establishment of the LDL profile.…”

Section: Discussionmentioning

confidence: 92%

Preferential cholesteryl ester acceptors among the LDL subspecies of subjects with familial hypercholesterolemia.

Guérin

Dolphin

Chapman

1994

Arterioscler Thromb

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Elevated cholesteryl ester transfer protein-mediated transfer of cholesteryl ester (CE) from high-density lipoprotein (HDL) to low-density lipoprotein (LDL) may contribute to the atherogenicity of LDL in subjects with familial hypercholesterolemia (FH). To identify the major CE acceptors among LDL subspecies, we investigated the qualitative and quantitative features of CE transfer and exchange to LDL on incubation of plasma under physiological conditions. LDL subspecies were fractionated by density-gradient ultracentrifugation. Both mass transfer and exchange of HDL CE to and with very-low-density lipoprotein plus intermediatedensity lipoprotein and LDL were linear for the first 6 hours of incubation. Thereafter mass transfer ceased, but exchange continued at a comparable rate. In plasma, LDL is distributed as a continuum of particles over the density range between d= 1.019 and d= 1.063 g/mL. In this density interval, multiple LDL subspecies possessing different physical, chemical, hydrodynamic, immunological, and structural properties have been described in the plasma of normolipidemic and hypercholesterolemic subjects. 1219 In this study, we determined both exchange and net mass transfer of CE from HDL to LDL subfractions by a methodology involving the simultaneous determination of CE radioactivity and mass in both normolipidemic and hypercholesterolemic subjects. We investigated possible relations between CE transfer and the establishment of the LDL profile in human plasma. Moreover, we identified which LDL subspecies may represent the preferential CE acceptors in patients with familial hypercholesterolemia (FH) compared with those in normolipidemic subjects. Elevated CE transfer to preferred LDL subspecies may represent a determinant factor in promoting the atherogenic LDL profile generally observed in FH patients. Methods Subjects and Blood SamplesApproval by the Human Subjects Review Committee of the hospital and informed consent from all participants was obtained. Six heterozygous FH subjects (4 men and 2 women) by guest on May 9, 2018 http://atvb.ahajournals.org/ Downloaded from

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Section: Discussionmentioning

confidence: 92%

Preferential cholesteryl ester acceptors among the LDL subspecies of subjects with familial hypercholesterolemia.

Guérin

Dolphin

Chapman

1994

Arterioscler Thromb

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“…16,17 The gels were stained with Coomassie G-250 (Nacalai). The distribution profile of LDL subfractions was determined by densitometric scanning of the gels at 633 nm (Shimadzu).…”

Section: Ldl Particle Diametermentioning

confidence: 99%

“…The apparent diameters of major LDL subfractions were measured by comparing results with a calibration curve constructed with ferritin, thyroglobulin, and latex beads. 17 …”

Section: Ldl Particle Diametermentioning

confidence: 99%

Different Effects of Oral Conjugated Equine Estrogen and Transdermal Estrogen Replacement Therapy on Size and Oxidative Susceptibility of Low-Density Lipoprotein Particles in Postmenopausal Women

et al. 2002

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Background-Postmenopausal estrogen replacement therapy (ERT) has an antioxidant effect that opposes the oxidation of LDL particles. Oral ERT-induced increases in plasma triglyceride, however, decrease LDL particle size, which may counteract this antioxidant effect. Because transdermal ERT decreases plasma triglyceride, it may not decrease LDL particle size and may preserve estrogen's antioxidant effect. The present study investigates whether transdermal ERT can eliminate the adverse effects of oral ERT on the size and oxidative susceptibility of LDL in postmenopausal women. Methods and Results-Postmenopausal women received no treatment (nϭ12) or were treated with either 0.625 mg oral conjugated equine estrogen daily (nϭ16) or with transdermal estradiol (50 g/d, nϭ16) for 3 months. Plasma lipids and the diameter of LDL particles were determined. Susceptibility of LDL to oxidation was analyzed by incubation with CuSO 4 and subsequent measurement of thiobarbituric acid reactive substance (TBARS) concentrations. Oral ERT significantly increased plasma triglyceride and decreased LDL diameter but did not affect LDL-derived TBARS concentrations. In contrast, transdermal ERT significantly decreased the concentrations of plasma triglyceride and LDL-derived TBARS and significantly increased LDL diameter. Estrogen-induced changes in LDL diameter correlated negatively with changes in plasma triglyceride (rϭϪ0.51, PϽ0.001) and LDL-derived TBARS (rϭϪ0.50, PϽ0.001). Conclusions-Because transdermal, but not oral ERT, decreases plasma triglyceride and produces larger LDL particles that are resistant to oxidation, the antioxidant effect of estrogen can be preserved.

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“…[13][14][15] Similarly, there is evidence that CETP may play a role in LDL size determination. 16,17 To examine the linkage of LDL particle size with the CETP gene, we have identified a highly informative tetranucleotide repeat within the CETP gene promoter and used it in quantitative sib-pair linkage analysis in the DZ twins of the Kaiser Permanente Women Twins Study. 18 …”

mentioning

confidence: 99%

Linkage of the Cholesteryl Ester Transfer Protein ( CETP ) Gene to LDL Particle Size

et al. 2000

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Background-A preponderance of small, dense LDL particles, elevated levels of plasma triglycerides (TG), and low levels of HDL characterize the atherogenic lipoprotein phenotype, which is associated with increased coronary artery disease (CAD) risk. Genetic and environmental factors influence LDL size, cholesteryl ester transfer protein (CETP) being one of the candidate genes. CETP mediates the transfer of cholesteryl ester from HDL to apolipoprotein (apo) B-containing lipoproteins in exchange for TG, promoting reverse cholesterol transfer and remodeling of lipoprotein particles. Methods and Results-We have identified a tetranucleotide repeat (fragment sizes from 324 to 464 bp; heterozygosity indexϭ0.74) within the CETP promoter and used it in quantitative sib-pair linkage analysis in 119 female dizygotic (DZ) twins. Linkage was found to LDL size (PϽ0.001), TG (PϽ0.005), and plasma apoB (Pϭ0.02). The distribution of the tetranucleotide repeats was bimodal, and there was strong allelic association of the "short" alleles with the B2 allele of CETP TaqIB polymorphic site (PϽ0.001). Conclusions-This report of linkage of the CETP gene to LDL particle size adds to the list of candidate genes linked to LDL size, supporting the hypothesis of multigenic determination of LDL size heterogeneity. Whether this promoter variation is itself functional or is a marker for a functional site in the CETP gene remains to be determined. (Circulation.

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Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects.

Cited by 115 publications

References 59 publications

Preferential cholesteryl ester acceptors among the LDL subspecies of subjects with familial hypercholesterolemia.

Preferential cholesteryl ester acceptors among the LDL subspecies of subjects with familial hypercholesterolemia.

Different Effects of Oral Conjugated Equine Estrogen and Transdermal Estrogen Replacement Therapy on Size and Oxidative Susceptibility of Low-Density Lipoprotein Particles in Postmenopausal Women

Linkage of the Cholesteryl Ester Transfer Protein ( CETP ) Gene to LDL Particle Size

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