Journal
ATHEROSCLEROSIS
Volume 221, Issue 1, Pages 160-168Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2011.12.027
Keywords
CETP; High density lipoprotein; Cellular cholesterol efflux; HDL-CE uptake
Funding
- INSERM
- UPMC
- Pfizer
- French Ministry of Research and Technology
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Objective: To evaluate the impact of CETP inhibition on the capacity of individual postprandial HDL subspecies to promote key steps of the reverse cholesterol transport pathway. Methods: The capacity of HDL particles to mediate cellular free cholesterol efflux and selective hepatic uptake of cholesteryl esters was evaluated throughout postprandial phase (0-8 h) following consumption of a standardised mixed meal before and after treatment for 6 weeks with atorvastatin alone (10 mg/d) and subsequently with combination torcetrapib/atorvastatin (60/10 mg/d) in 16 patients displaying low HDL-C levels (<40 mg/dl). Results: The larger HDL2b and HDL2a subfraction displayed a superior capacity to mediate cellular free cholesterol efflux via both SR-BI and ABCG1-dependent pathways than smaller HDL3 subspecies. CETP inhibition specifically enhanced the capacity of HDL2b subfraction for both SR-BI and ABCG1 dependent efflux. However, only the SR-BI-dependent efflux to HDL2b subspecies can be further enhanced during postprandial lipemia following CETP inhibition. Concomitantly, postprandial lipemia was associated with a reduced capacity of total HDL particles to deliver cholesteryl esters to hepatic cells in a drug independent manner. Conclusion: CETP inhibition specifically improves postprandial SR-BI and ABCG1-dependent efflux to larger HDL2b subspecies. In addition, CETP inhibition improves HDL-CE delivery to hepatic cells and maintains an efficient direct return of cholesteryl esters to the liver during postprandial lipemia. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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