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

TLDR

Macrophage scavenger receptors are key contributors to atherosclerosis development. The study aimed to determine the role of the class B scavenger receptor CD36 in atherogenesis. This was investigated by crossing a CD36‑null strain with an atherogenic apo E‑null strain and quantifying lesion development. CD36‑apo E double‑null mice showed a 76.5 % reduction in aortic‑tree lesions on a Western diet and a 45 % reduction in aortic‑sinus lesions on normal chow, while their macrophages internalized more than 60 % less oxidized LDL and LDL modified by reactive nitrogen species, resulting in decreased lipid accumulation and foam‑cell formation, thereby confirming CD36’s pivotal role in atherosclerosis and indicating that its blockade can be protective even under severe proatherogenic conditions.

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.