Serum amyloid A promotes cholesterol efflux mediated by scavenger receptor B-I

Deneys R. Van Der Westhuyzen, Lei Cai, Maria C. De Beer, Frederick C. De Beer

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Serum amyloid A (SAA) is an acute phase protein whose expression is markedly up-regulated during inflammation and infection. The physiological function of SAA is unclear. In this study, we reported that SAA promotes cellular cholesterol efflux mediated by scavenger receptor B-I (SR-BI). In Chinese hamster ovary cells, SAA promoted cellular cholesterol efflux in an SR-BI-dependent manner, whereas apoA-I did not. Similarly, SAA, but not apoA-I, promoted cholesterol efflux from HepG2 cells in an SR-BI-dependent manner as shown by using the SR-BI inhibitor BLT-I. When SAA was overexpressed in HepG2 cells using adenovirus-mediated gene transfer, the endogenously expressed SAA promoted SR-BI-dependent efflux. To assess the effect of SAA on SR-BI-mediated efflux to high density lipoprotein (HDL), we compared normal HDL, acute phase HDL (AP-HDL, prepared from mice injected with lipopolysaccharide), and AdSAA-HDL (HDL prepared from mice overexpressing SAA). Both AP-HDL and AdSAA-HDL promoted 2-fold greater cholesterol efflux than normal HDL. Lipid-free SAA was shown to also stimulate ABCA1-dependent cholesterol efflux in fibroblasts, in line with an earlier report (Stonik, J. A., Remaley, A. T., Demosky, S. J., Neufeld, E. B., Bocharov, A., and Brewer, H. B. (2004) Biochem. Biophys. Res. Commun. 321, 936-941). When added to cells together, SAA and HDL exerted a synergistic effect in promoting ABCA1-dependent efflux, suggesting that SAA may remodel HDL in a manner that releases apoA-I or other efficient ABCA1 ligands from HDL. SAA also facilitated efflux by a process that was independent of SR-BI and ABCA1. We conclude that the acute phase protein SAA plays an important role in HDL cholesterol metabolism by promoting cellular cholesterol efflux through a number of different efflux pathways.

Original languageEnglish
Pages (from-to)35890-35895
Number of pages6
JournalJournal of Biological Chemistry
Volume280
Issue number43
DOIs
StatePublished - Oct 28 2005

Bibliographical note

Funding Information:
Manuscript received December 28, 1999; accepted April 30, 2000. From the Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand. This work was partially funded by the Swiss National Science Foundation and the Health Research Council of New Zealand. Address for reprint requests: Professor Gilbert Barbezat, Department of Medicine, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin, New Zealand.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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