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Atheroprotective Reverse Cholesterol Transport Pathway Is Defective in Familial Hypercholesterolemia.
MedLine Citation:
PMID:  21527752     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: Low high-density lipoprotein (HDL) cholesterol levels are frequently observed in familial hypercholesterolemia (FH) and might be associated with functional alterations of HDL particles that may influence their efficaciousness in the reverse cholesterol transport pathway. METHODS AND RESULTS: We evaluated key steps of the reverse cholesterol transport, ie, cellular free cholesterol efflux, CETP-mediated cholesteryl ester (CE) transfer from HDL to apolipoprotein B-containing lipoproteins, and hepatic HDL-CE uptake, in patients displaying FH (n=12) and in healthy normolipidemic control subjects (n=12). Large HDL2 particles isolated from FH patients displayed a reduced capacity to mediate free cholesterol efflux via both scavenger receptor-BI- and ABCG1-dependent pathways. A significant inverse relationship between scavenger receptor-BI-dependent HDL2 efflux capacity and carotid intima-media thickness (r=-0.473; P=0.0186), as well as between ABCG1-dependent HDL2 efflux capacity and carotid intima-media thickness (r=-0.485; P=0.0212), was detected. We also observed an elevated CETP-mediated CE transfer from HDL2 and HDL3 particles to low-density lipoprotein and a reduced capacity of HDL particles to deliver CEs to the liver. CONCLUSIONS: We demonstrated that the centripetal movement of cholesterol from peripheral tissues, including the vessel wall, to feces is defective in FH, thereby emphasizing its atherogenicity.
Authors:
Natacha Bellanger; Alexina Orsoni; Zélie Julia; Natalie Fournier; Eric Frisdal; Emilie Duchene; Eric Bruckert; Alain Carrie; Dominique Bonnefont-Rousselot; John Pirault; Flora Saint-Charles; M John Chapman; Philippe Lesnik; Wilfried Le Goff; Maryse Guerin
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-28
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  -     ISSN:  1524-4636     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institut National de la Santé et de la Recherche Médicale, UMRS 939.
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