PPAR-GAMMA PROMOTES MONOCYTE MACROPHAGE DIFFERENTIATION AND UPTAKE OFOXIDIZED LDL/

The formation of foam cells from macrophages in the arterial wall is c haracterized by dramatic changes in lipid metabolism, including increa sed expression of scavenger receptors and the uptake of oxidized low-d ensity lipoprotein (oxLDL). We demonstrate here that the nuclear recep tor PPAR gamma is induced in human monocytes following exposure to oxL DL and is expressed at high levels in the foam cells of atheroscleroti c lesions. Ligand activation of the PPBR gamma:RXR alpha heterodimer i n myelomonocytic cell lines induces changes characteristic of monocyti c differentiation and promotes uptake of oxLDL through transcriptional induction of the scavenger receptor CD36. These results reveal a nove l signaling pathway controlling differentiation and lipid metabolism i n monocytic cells, and suggest that endogenous PPAR gamma ligands may be important regulators of gene expression during atherogenesis.