Absence of CD36 protects against atherosclerosis in ApoE knock-out mice with no additional protection provided by absence of scavenger receptor A I/II

Aims The role of scavenger receptors in atherogenesis is controversial as a result of conflicting reports and a recent hypothesis suggesting that scavenger receptor absence would enhance the pro-inflammatory, pro-atherogenic milieu. This study addresses the effect of combined absence of scavenger receptors CD36 and SRA I/II on atherosclerosis lesion development in the apolipoprotein E knock-out (apoE degrees) model. Methods We created background-related strains of apoE degrees, scavenger receptor A I/II knock-out (SRA degrees)/apoE degrees, CD36 knock-out (CD36 degrees)/apoE degrees, and CD36 degrees/SRA degrees/apoE degrees mice that were >99% C57BL/6. Four-week-old mice were fed a Western diet for 12 weeks and were assessed for lesion burden/morphology, risk factors for atherosclerosis, inflammatory mediators, and macrophage function. Results There was a 61 and 74% decrease in total aortic lesion area in CD36 degrees/apoE degrees mates and females, respectively, compared with apoE degrees controls. The absence of SRA was protective (32% decrease in lesion) in female mice. The combined absence of CD36 and SRA provided no further protection in either gender. Macrophages from mice lacking CD36 had decreased pro-inflammatory characteristics and less migration to a pro-inflammatory stimulus. Plasma levels of cytokines/chemokines showed that CD36 degrees/apoE degrees and CD36 degrees/SRA degrees/apoE degrees mice had a less pro-inflammatory phenotype compared with apoE degrees and SRA degrees/apoE degrees mice. Oblivious mice in the apoE degrees background ruled out potential 'passenger gene' effects in the case of CD36. Conclusion These results provide new insights into the pro-atherogenic mechanisms of CD36 by implicating processes other than modified lipoprotein uptake.