Objective: To investigate the mechanisms by which macrophage scavenger receptor BI (SR-BI) regulates macrophage cholesterol homeostasis and protects against atherosclerosis. Methods and results: The expression and function of SR-BI was investigated in cultured mouse bone marrow-derived macrophages (BMM). SR-BI, the other scavenger receptors SRA and CD36 and the ATP-binding cassette transporters ABCA1 and ABCG1 were each distinctly regulated during BMM differentiation. SR-BI levels increased transiently to significant levels during culture. SR-BI expression in BMM was reversibly down-regulated by lipid loading with modified LDL; SR-BI was shown to be present both on the cell surface as well as intracellularly. BMM exhibited selective HDL CE uptake, however, this was not dependent on SR-BI or another potential candidate glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1). SR-BI played a significant role in facilitating bidirectional cholesterol flux in non lipid-loaded cells. SR-BI expression enhanced both cell cholesterol efflux and cholesterol influx from HDL, but did not lead to altered cellular cholesterol mass. SR-BI-dependent efflux occurred to larger HDL particles but not to smaller HDL 3. Following cholesterol loading, ABCA1 and ABCG1 were up-regulated and served as the major contributors to cholesterol efflux, while SR-BI expression was down-regulated. Conclusion: Our results suggest that SR-BI plays a significant role in macrophage cholesterol flux that may partly account for its effects on atherogenesis.
|Number of pages||7|
|State||Published - Jul 2011|
Bibliographical noteFunding Information:
The authors would like to thank Xuebing Wang, Xin Shi, Kathy Forrest and Susan Bridges for excellent technical support. The ABCA1 antibody was generously provided by Dr Michael Hayden. This work was supported by a National Institutes of Health Program Project Grant (PO1HL086670) to D. R. van der Westhuyzen.
- Cholesterol efflux
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine