TY - JOUR
T1 - High-Density Lipoprotein (HDL) Particle Subpopulations in Heterozygous Cholesteryl Ester Transfer Protein (CETP) Deficiency: Maintenance of Antioxidative Activity
AU - Chantepie, Sandrine
AU - Bochem, Andrea E.
AU - Chapman, M. John
AU - Hovingh, G. Kees
AU - Kontush, Anatol
PY - 2012
Y1 - 2012
N2 - 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
AB - 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
U2 - https://doi.org/10.1371/journal.pone.0049336
DO - https://doi.org/10.1371/journal.pone.0049336
M3 - Article
C2 - 23189141
SN - 1932-6203
VL - 7
SP - e49336
JO - PLOS ONE
JF - PLOS ONE
IS - 11
ER -