Expression of the peroxisome proliferator-activated receptor γ (PPARγ) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein

The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand dependent transcription factor that has been demonstrated to regulate fat cell development and glucose homeostasis. PPAR gamma is also expressed in a subset of macrophages and negatively regulates the expression of several proinflammatory genes in response to natural and synthetic ligands, We here demonstrate that PPAR gamma is expressed in macrophage foam cells of human atherosclerotic lesions, in a pattern that is highly correlated with that of oxidation-specific epitopes, Oxidized low density lipoprotein (oxLDL) and macrophage colony-stimulating factor, which are known to be present in atherosclerotic lesions, stimulated PPAR gamma expression in primary macrophages and monocytic cell lines. PPAR gamma mRNA expression was also induced in primary macrophages and THP-1 monocytic leukemia cells by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). inhibition of protein kinase C blocked the induction of PPAR gamma expression by TPA, but not by oxLDL, suggesting that more than one signaling pathway regulates PPAR gamma expression in macrophages, TPA induced the expression of PPAR gamma in RAW 264.7 macrophages by increasing transcription from the PPAR gamma 1 and PPAR gamma 3 promoters. in concert, these observations provide insights into the regulation of PPAR gamma expression in activated macrophages and raise the possibility that PPAR gamma ligands mag influence the progression of atherosclerosis.