title: High-density lipoprotein (HDL) particle subpopulations in heterozygous cholesteryl ester transfer protein (CETP) deficiency: maintenance of antioxidative activity.
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.
authors.affiliation: INSERM UMRS 939, Pitie-Salpetriere University Hospital, Paris, France. sandrine.chantepie@u-pec.fr
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chantepie
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Bochem
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
chemical_list: D000975:Antioxidants; D053480:Cholesterol Ester Transfer Proteins; D008075:Lipoproteins, HDL