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

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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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Figure 1

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Disruption of CD36 decreases atherosclerotic lesion development in apo E...
Disruption of CD36 decreases atherosclerotic lesion development in apo E–null mice. Circles, apo E-null male (n = 9); squares, CD36-apo E double-null male (n = 5); triangle, apo E–null female (n = 5); reversed triangle, CD36-apo E double-null female (n = 6). (a) Lesion surface area in the aortic tree was assessed by en face oil red-O positive staining. The aortic tree from the heart to below the bifurcation of the iliac arteries was removed and dissected for staining and lesion analysis from mice fed a Western diet for 12 weeks. Each sample was scanned, and total oil red-O positive area was determined using Scion Image software. AP < 0.001, BP < 0.001, Mann-Whitney test. (b) Aortic sinus cross-sectional lesion area was measured in mice fed the atherogenic Western diet for 12 weeks. Atherosclerotic plaque area was determined by oil red-O positivity and morphology and measured using NIH Image software. CP < 0.0005, Mann Whitney test. (c) Prevalence of lesions at different sites in the aortic tree. En face oil red-O positive lesions from a were assessed in 3 regions of the aorta, aortic arch, thoracic-abdominal aorta, and at the iliac bifurcation, and lesion area was expressed as percent of total area of that site. (d) Aortic sinus lesion area measured as in b in mice fed a normal chow diet. Mice were 16 weeks old at sacrifice. Apo E–null male (n = 11); CD36-apo E double-null male (n = 9); apo E–null female (n = 9); CD36-apo E double-null female (n = 13). DP < 0.01, Mann Whitney test.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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