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

• Published in: Circulation (New York, N.Y.) N.Y.), 2003-11, Vol.108 (18), p.2258-2263
• Main Authors: WENWU ZHANG, YANCEY, Patricia G, YAN RU SU, BABAEV, Vladimir R, YUOMIN ZHANG, FAZIO, Sergio, LINTON, Macrae F
• Format: Article
• Language: English
• Subjects: Animals; Aorta - pathology; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Arteriosclerosis - genetics; Arteriosclerosis - pathology; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - biosynthesis; Biological and medical sciences; Blood and lymphatic vessels; Blotting, Western; Bone Marrow Transplantation; Cardiology. Vascular system; CD36 Antigens - biosynthesis; CD36 Antigens - genetics; Cells, Cultured; Cholesterol - metabolism; Disease Models, Animal; Disease Progression; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Lipoproteins, HDL - blood; Macrophages, Peritoneal - metabolism; Medical sciences; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Radiation Chimera; Receptors, Immunologic; Receptors, Lipoprotein; Receptors, Scavenger; Scavenger Receptors, Class B
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.0000093189.97429.9d

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. 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. 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.