Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice
Maria Febbraio, … , Kavita Sharma, Roy L. Silverstein
Maria Febbraio, … , Kavita Sharma, Roy L. Silverstein
Published April 15, 2000
Citation Information: J Clin Invest. 2000;105(8):1049-1056. https://doi.org/10.1172/JCI9259.
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Article

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

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.

Authors

Maria Febbraio, Eugene A. Podrez, Jonathan D. Smith, David P. Hajjar, Stanley L. Hazen, Henry F. Hoff, Kavita Sharma, Roy L. Silverstein

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Atherosclerotic lesion distribution and morphology is altered in CD36-de...
Atherosclerotic lesion distribution and morphology is altered in CD36-deficient mice. The entire aorta from apo E–null (a) and CD36-apo E double-null (b) mice were dissected and opened longitudinally. Oil red-O–stained lesions occur in all regions of the aorta from the apo E–null mouse, whereas in the aorta from the CD36-apo E double-null mouse lesions are seen primarily in the aortic arch. ×20. Hearts were dissected from apo E–null (c) and CD36-apo E double-null (d) mice fed a normal chow diet, cryosectioned at the level of the valve leaflets, and stained with oil red-O and fast green. Lesions in apo E–null mice contained lipid-laden, intensely oil red-O–stained foam cells, cellular areas of less oil red-O positivity, empty spaces, and cholesterol clefts. Those in CD36-apo E double-null mice contained only rare areas lacking cells or containing cholesterol clefts. ×250.