on January 12, 2006
Published online before print January 12, 2006, doi: 10.1161/01.ATV.0000203515.25574.19
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Submitted on August 23, 2005
Accepted on December 23, 2005
Relative Contributions of ABCA1 and SR-BI to Cholesterol Efflux to Serum From Fibroblasts and Macrophages
MyNgan Duong ;
From GI and Nutrition (M.D., H.L.C., G.H.R.), The Children’s Hospital of Philadelphia, Philadelphia, Pa; the School of Medicine (W.J.), University of Pennsylvania, Philadelphia, Pa; and the Department of Pharmacological and Biological Sciences and Applied Chemistries (I.Z., E.F.), University of Parma, Italy.
* To whom correspondence should be addressed. E-mail: rothblat{at}email.chop.edu.
Objectives--Cholesterol efflux is achieved by several mechanisms. This study examines contributions of these pathways to efflux to human serum.
Methods and Results--Human fibroblasts were stably transfected with SR-BI while ABCA1 was upregulated. Quantitation of cholesterol efflux to human serum demonstrated that there was efflux from cells without either protein. Expression of ABCA1 produced a small increase in efflux, whereas SR-BI expression had a dramatic impact. To quantitate ABCA1 and SR-BI contribution, fibroblasts were pretreated with Probucol and BLT-1 to, respectively, inhibit these efflux proteins. Exposing SR-BI-expressing fibroblast to BLT-1 inhibited efflux by 67%. Probucol pretreatment of ABCA1-expressing fibroblast reduced efflux to serum by 26%. A large fraction of total efflux was uninhibited. For both J774 and mouse peritoneal macrophages, contributions of either ABCA1 or SR-BI to efflux to serum were low, with background/uninhibited efflux contributing from 70% to 90% of total efflux.
Conclusions--We have shown that ABCA1-mediated efflux to serum responds to the pool of lipid-free/poor apolipoproteins, whereas phospholipid-containing particles mediate SR-BI efflux. Although SR-BI and ABCA1 contribute to efflux from fibroblasts and cholesterol-enriched macrophages, a large proportion of the total efflux to human serum is mediated by a mechanism that is neither SR-BI nor ABCA1.
Key words: ABCA1 • cholesterol efflux • fibroblasts • macrophage • SR-BI
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