High-Density Lipoprotein (HDL) Particle Subpopulations in Heterozygous Cholesteryl Ester Transfer Protein (CETP) Deficiency: Maintenance of Antioxidative Activity

Sandrine Chantepie, Andrea E. Bochem, M. John Chapman, G. Kees Hovingh, Anatol Kontush

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33 Citations (Scopus)

Abstract

Cholesteryl ester transfer protein (CETP) deficiency causes elevated high-density lipoprotein-cholesterol (HDL-C) levels; its impact on HDL functionality however remains elusive. We compared functional and compositional properties of HDL derived from 9 Caucasian heterozygous CETP mutation carriers (splice-site mutation in intron 7 resulting in premature truncation) with those of 9 age-and sex-matched normolipidemic family controls. As expected, HDL-C levels were increased 1.5-fold, and CETP mass and activity were decreased by -31% and -38% respectively, in carriers versus non-carriers. HDL particles from carriers were enriched in CE (up to +19%, p <0.05) and depleted of triglycerides (TG; up to -54%, p <0.01), resulting in a reduced TG/CE ratio (up to 2.5-fold, p <0.01). In parallel, the apoA-I content was increased in HDL from carriers (up to +22%, p <0.05). Both the total HDL fraction and small, dense HDL3 particles from CETP-deficient subjects displayed normal antioxidative activity by attenuating low-density lipoprotein oxidation with similar efficacy on a particle mass basis as compared to control HDL3. Consistent with these data, circulating levels of systemic biomarkers of oxidative stress (8-isoprostanes) were similar between the two groups. These findings support the contention that HDL functionality is maintained in heterozygous CETP deficiency despite modifications in lipid and protein composition
Original languageEnglish
Pages (from-to)e49336
JournalPLOS ONE
Volume7
Issue number11
DOIs
Publication statusPublished - 2012

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