Absence of CD36 is Protective at Late Time Points in the apoE Knockout (KO), and Additional Absence of Scavenger Receptor A I/II (SRA) Provides no Added Benefit

Previously, absence of the scavenger receptor CD36 or SRA was shown to be protective against atherosclerosis in the apoE KO after 12 weeks on western diet. A recent report (JCI 115. 2192 (2005)) showed no effect for SRA, and protection in females only for CD36 by en face analysis after 8 weeks on western diet. Here we determined if combined absence of CD36 and SRA had greater effect in the apoE KO. We analyzed lesions from CD36/apo E double KOs (dkos) and SRA/apoE dkos as controls. These mice are derived from those used in the JCI study. Because atherosclerosis is a multistep process involving many different factors over time, we also investigated whether absence of CD36 was protective at later time points in the apoE KO. Methods For the tko study, mice were on western diet for 12 weeks; for the long term study, mice were on diet for 20 and 35 weeks. Aortas were dissected and subjected to en face analysis. After 12 weeks on diet, tko males had 58% less lesion area compared with apoE KO males; tko females had 63% less lesion area. Male CD36/apoE dkos had 61% less lesion compared with apoE KO males; CD36/apoE dko females had 81% less lesion. These results indicate no added benefit to absence of SRA compared with absence of CD36 alone in this model. At 20 and 35 weeks, lesions were 25–28% smaller in the CD36/apoE dkos compared to apoE KOs. However, most impressive here was the difference in the gross appearance of the aortas: the apoE KO aortas were sclerotic and nearly occluded by lesion, whereas in the CD36/apoE dkos, the lesions were more punctate. Funding : NIH HL70083, HL072942 , & HL46403