Dual Role for Scavenger Receptor Class B, Type I on Bone Marrow-Derived Cells in Atherosclerotic Lesion Development

• Published in: The American journal of pathology Vol. 165; no. 3; pp. 785 - 794
• Main Authors: Van Eck, Miranda, Bos, I. Sophie T., Hildebrand, Reeni B., Van Rij, Brechje T., Van Berkel, Theo J.C.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.09.2004; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Arteriosclerosis - metabolism; Arteriosclerosis - pathology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Cardiology. Vascular system; CD36 Antigens; Cholates - metabolism; Cholesterol, Dietary; Diet, Atherogenic; Female; Homozygote; Investigative techniques, diagnostic techniques (general aspects); Lipid Metabolism; Lipoproteins, LDL - metabolism; Macrophages - physiology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Rats; Receptors, Immunologic - genetics; Receptors, Immunologic - physiology; Receptors, LDL - genetics; Receptors, LDL - physiology; Receptors, Scavenger; Regular; Scavenger Receptors, Class B; Vascular disease; Cell proliferation; Scavenger receptor; Anatomic pathology; Atherosclerosis; Bone marrow; Cardiovascular disease; Lesion
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)63341-X

The function of scavenger receptor class B, type I (SR-BI) in the liver as a high-density lipoprotein receptor that promotes the selective uptake of cholesteryl esters is well defined. Its role in macrophages, however, is primarily unknown, because it functions in the uptake of (modified) lipoproteins as well as the secretion of cholesterol to high-density lipoproteins. In this study, the biological role of SR-BI on bone marrow-derived cells, including macrophages, in lipid metabolism and atherosclerosis was assessed by selective disruption of SR-BI in bone marrow in two established models of atherosclerosis: low-density lipoprotein (LDL) receptor-deficient mice that develop extensive atherosclerosis on a Western-type diet and wild-type mice that develop fatty streak lesions when fed a high-cholesterol diet containing 0.5% cholate. The presence of SR-BI in bone marrow-derived cells in LDLr−/− mice decreased lesion development after 9 and 12 weeks of Western-type diet feeding, indicating that macrophage SR-BI protects against lesion development. At 6 weeks, no significant effect of SR-BI in bone marrow-derived cells on lesion development was observed. Interestingly, after only 4 weeks of Western-type diet feeding of transplanted LDLr−/− mice and in wild-type mice on a high-cholesterol/cholate diet, the presence of SR-BI in bone marrow-derived cells increased the development of small fatty streak lesions. It thus appears that, depending on the stage of atherosclerotic lesion development, SR-BI in bone marrow-derived cells is either pro-atherogenic or anti-atherogenic, indicating a unique dual role in the pathogenesis of atherosclerosis.