Format

Send to

Choose Destination
Atherosclerosis. 2011 Jul;217(1):106-12. doi: 10.1016/j.atherosclerosis.2011.03.017. Epub 2011 Apr 9.

Scavenger receptor SR-BI in macrophage lipid metabolism.

Author information

1
Department of Internal Medicine, University of Kentucky, Lexington, KY 40536, USA. ailing.ji@uky.edu

Abstract

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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center