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Functionality of postprandial larger HDL2 particles is enhanced following CETP inhibition therapy.
MedLine Citation:
PMID:  22265126     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 (0-8h) following consumption of a standardised mixed meal before and after treatment for 6 weeks with atorvastatin alone (10mg/d) and subsequently with combination torcetrapib/atorvastatin (60/10mg/d) in 16 patients displaying low HDL-C levels (<40mg/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.
Authors:
Natacha Bellanger; Zélie Julia; Elise F Villard; Petra El Khoury; Emilie Duchene; M John Chapman; Natalie Fournier; Wilfried Le Goff; Maryse Guerin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-4
Journal Detail:
Title:  Atherosclerosis     Volume:  -     ISSN:  1879-1484     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
INSERM UMRS939, Hôpital de la Pitié, Paris, France; Université Pierre et Marie Curie-Paris 6, UMRS939, Paris, France.
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