Inactivation of macrophage scavenger receptor class B type I promotes atherosclerotic lesion development in apolipoprotein E-deficient mice.

Zhang W, Yancey PG, Su YR, Babaev VR, Zhang Y, Fazio S, Linton MF
Circulation. 2003 108 (18): 2258-63

PMID: 14581413 · DOI:10.1161/01.CIR.0000093189.97429.9D

BACKGROUND - Scavenger receptor class B type I (SR-BI) is expressed in macrophages, where it has been proposed to facilitate cholesterol efflux. However, direct evidence that the expression of macrophage SR-BI is protective against atherosclerosis is lacking. In this study, we examined the in vivo role of macrophage SR-BI in atherosclerotic lesion development in the apolipoprotein (apo) E-deficient mouse model.

METHODS AND RESULTS - ApoE-deficient mice with (n=16) or without (n=15) expression of macrophage SR-BI were created by transplanting lethally irradiated apoE-deficient mice with bone marrow cells collected from SR-BI-/- apoE-/- mice or SR-BI+/+ apoE-/- mice. The recipient mice were fed a chow diet for 12 weeks after transplantation for analysis of atherosclerosis. Quantification of macrophage SR-BI mRNA by real-time reverse transcription-polymerase chain reaction indicated successful engraftment of donor bone marrow and inactivation of macrophage SR-BI in recipient mice reconstituted with SR-BI-/- apoE-/- bone marrow. There were no significant differences in plasma lipid levels, lipoprotein distributions, and HDL subpopulations between the 2 groups. Analysis of the proximal aorta demonstrated an 86% increase in mean atherosclerotic lesion area in SR-BI-/- apoE-/- --> apoE-/- mice compared with SR-BI+/+ apoE-/- --> apoE-/- mice (109.50+/-18.08 versus 58.75+/-9.58x10(3) microm2; mean+/-SEM, P=0.017). No difference in cholesterol efflux from SR-BI+/+ apoE-/- or SR-BI-/- apoE-/- macrophages to HDL or apoA-I discs was detected.

CONCLUSIONS - Expression of macrophage SR-BI protects mice against atherosclerotic lesion development in apoE-deficient mice in vivo without influencing plasma lipids, HDL subpopulations, or cholesterol efflux. Thus, macrophage SR-BI plays an antiatherogenic role in vivo, providing a new therapeutic target for the design of strategies to prevent and treat atherosclerosis.

MeSH Terms (25)

Animals Aorta Apolipoproteins E Arteriosclerosis ATP-Binding Cassette Transporters ATP Binding Cassette Transporter 1 Blotting, Western Bone Marrow Transplantation CD36 Antigens Cells, Cultured Cholesterol Disease Models, Animal Disease Progression Female Lipoproteins, HDL Macrophages, Peritoneal Membrane Proteins Mice Mice, Inbred C57BL Mice, Knockout Radiation Chimera Receptors, Immunologic Receptors, Lipoprotein Receptors, Scavenger Scavenger Receptors, Class B

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