Faculty Collaboration Database

Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest 2000 Apr;105(8):1049-56

Date

04/20/2000

Pubmed ID

10772649

Pubmed Central ID

PMC300837

DOI

10.1172/JCI9259

Scopus ID

2-s2.0-0034101821 (requires institutional sign-in at Scopus site)   859 Citations

Abstract

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.

Author List

Febbraio M, Podrez EA, Smith JD, Hajjar DP, Hazen SL, Hoff HF, Sharma K, Silverstein RL

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Apolipoproteins E
Arteriosclerosis
CD36 Antigens
Cells, Cultured
Cholesterol
Female
Lipoproteins, LDL
Macrophages, Peritoneal
Male
Mice
Mice, Inbred C57BL
Receptors, Immunologic
Receptors, Scavenger
Triglycerides
Weight Gain