Inflammation, atherosclerosis, and arterial thrombosis: role of the scavenger receptor CD36

Abstract

The CD36 scavenger receptor recognizes oxidized low-density lipoprotein (LDL) and cell-derived microparticles. It is expressed on macrophages and platelets and is a mediator of both atherogenesis and thrombosis. Macrophages from CD36-null mice have a defect in foam cell formation in response to exposure to oxidized LDL, and CD36-null mice fed an atherogenic Western diet have significantly less atherosclerosis than their wild-type counterparts. On platelets, CD36 recognition of oxidized LDL contributes to their activation and provides a mechanistic link between hyperlipidemia, oxidant stress, and the prothrombotic state. Cell-derived microparticles are also major ligands for CD36 and contribute to thrombus formation in a CD36-dependent manner even in the absence of hyperlipidemia. CD36 deficiency in mice is associated with inhibition of thrombus formation and with a reduction in microparticle accumulation in thrombi. Targeting CD36 is a promising avenue for the treatment of atheroinflammatory disorders.

FIGURE 1

A mouse carotid artery (in cross section) injured with ferric chloride and then analyzed using immunofluorescent microscopy and an antibody to the endothelial cell–specific antigen CD105. The blue dots represent the nuclei in the vessel (stained with DAPI). In the top panel, a carotid thrombus in the lumen of a wild-type mouse is heavily enriched with CD105 (stained red), implying microparticle incorporation. In the CD36-null mouse (bottom panel), CD105 staining is decreased dramatically. The green staining represents an antibody to the platelet-specific antigen CD61.