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

Macrophage scavenger receptors have been implicated as key players in the p athogenesis of atherosclerosis. To assess the role of the class B scavenger receptor CD36 in atherogenesis, we crossed a CD35-null strain with the ath erogenic apo E-null strain and quantified lesion development. There was a 7 6.5% 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 mic e when compared with controls, despite alterations in lipoprotein profiles that often correlate with increased atherogenicity. Macrophages derived fro m CD36-apo E double-null mice bound and internalized more than 60% less cop per-oxidized LDL and LDL modified by monocyte-generated reactive nitrogen s pecies. A similar inhibition of in vitro lipid accumulation and foam cell f ormation after exposure to these Ligands was seen. These results support a major role for CD36 in atherosclerotic lesion development in vivo and sugge st that blockade of CD36 can be protective even in more extreme proatheroge nic circumstances.