Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice

• Published in: The Journal of clinical investigation Vol. 105; no. 8; pp. 1049 - 1056
• Main Authors: Febbraio, M, Podrez, E A, Smith, J D, Hajjar, D P, Hazen, S L, Hoff, H F, Sharma, K, Silverstein, R L
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 15-04-2000
• Subjects: Animals; Apolipoproteins E - genetics; Apolipoproteins E - physiology; Arteriosclerosis - etiology; Arteriosclerosis - prevention & control; CD36 Antigens - genetics; CD36 Antigens - physiology; Cells, Cultured; Cholesterol - blood; Female; Lipoproteins, LDL - metabolism; Macrophages, Peritoneal - cytology; Male; Mice; Mice, Inbred C57BL; Receptors, Immunologic - antagonists & inhibitors; Receptors, Immunologic - genetics; Receptors, Immunologic - physiology; Receptors, Scavenger; Triglycerides - blood; Weight Gain
• ISSN: 0021-9738
• DOI: 10.1172/jci9259

Macrophage scavenger receptors have been implicated as key players in the pathogenesis of atherosclerosis. To assess the role of the class B scavenger receptor CD36 in atherogenesis, we crossed a CD36-null strain with the atherogenic apo E-null strain and quantified lesion development. There was a 76.5% decrease in aortic tree lesion area (Western diet) and a 45% decrease in aortic sinus lesion area (normal chow) in the CD36-apo E double-null mice when compared with controls, despite alterations in lipoprotein profiles that often correlate with increased atherogenicity. Macrophages derived from CD36-apo E double-null mice bound and internalized more than 60% less copper-oxidized LDL and LDL modified by monocyte-generated reactive nitrogen species. A similar inhibition of in vitro lipid accumulation and foam cell formation after exposure to these ligands was seen. These results support a major role for CD36 in atherosclerotic lesion development in vivo and suggest that blockade of CD36 can be protective even in more extreme proatherogenic circumstances.