CD36-mediated macrophage foam cell formation. In response to EC injury, macrophages and LDL transmigrate into the subendothelial space (I), where they may become entrapped. Inflammatory stimuli (II) lead to the secretion of oxidative products from ECs and macrophages, including nitric oxide (NO), hydrogen peroxide, and myeloperoxidase (MPO) (III), which act upon LDL particles and convert them into CD36-specific ligands, or ligands for other scavenger receptors (SR). Internalization of oxidized LDL via CD36 (IV) generates lipid byproducts (e.g., 9-HODE, 13-HODE, and PGJ2), mediated by lipoxygenase or other pathways, which in turn provide ligands for the transcription factor PPARγ (V). The binding of these lipids structurally enables PPARγ to dimerize with binding partners such as RXR and charges the complex for nuclear translocation and the activation of transcription of target genes (VI). Because these target genes include both PPARγ and CD36, a positive feedback loop arises. The increased expression of CD36 promotes further oxidized LDL uptake, perpetuating the cycle and resulting in accumulation of cholesterol ester by macrophages and eventually in foam cell formation (VII). Adapted from ref. 48.