Relative contributions of ABCA1 and SR-BI to cholesterol efflux to serum from fibroblasts and macrophages

My Ngan Duong, Heidi L. Collins, Weijun Jin, Ilaria Zanotti, Elda Favari, George H. Rothblat

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90 Citations (Scopus)

Abstract

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 fibroblasts to BLT-1 inhibited efflux by 67%. Probucol pretreatment of ABCA1-expressing fibroblasts 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.

Original languageEnglish
Pages (from-to)541-547
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume26
Issue number3
DOIs
Publication statusPublished or Issued - Mar 2006

Keywords

  • ABCA1
  • Cholesterol efflux
  • Fibroblasts
  • Macrophage
  • SR-BI

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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