A. J. Belanger, H. Lu, T. Date, L. X. Liu, K. A. Vincent, G. Y. Akita, S. H. Cheng, R. J. Gregory and C. Jiang. Hypoxia Up-regulates Expression of Peroxisome Proliferator-activated Receptor γ Angiopoietin-related Gene (PGAR) in Cardiomyocytes: Role of Hypoxia Inducible Factor 1α. Journal of Molecular and Cellular Cardiology (2002)34 , 765–774. Peroxisome proliferator-activated receptors (PPAR), especially the PPARα and PPARγ, are associated with an extraordinary diverse spectrum of cardiovascular diseases including hypertension, angiogenesis, cardiac hypertrophy, and atherosclerosis. PGAR (for PPARγ angiopoietin-related gene) is a recently identified PPAR target gene which is associated with adipose differentiation, systemic lipid metabolism, energy homeostasis, and possibly angiogenesis. We report here that WY-14643, a selective PPARα ligand up-regulated PGAR expression in neonatal rat cardiomyocytes. In parallel to activating the expression of vascular endothelial growth factor and glucose transporter-4, hypoxia increased PGAR mRNA levels. PGAR expression was also increased by desferrioxamine and CoCl₂, but not by sodium cyanide, results consistent with the pharmacological features of hypoxia-responsive genes. These studies are the first to demonstrate that hypoxia increases the mRNA levels of a PPAR target gene in cardiomyocytes. Furthermore, infection with adenoviral vectors encoding the wild-type or a hybrid form of HIF-1α highly increased PGAR mRNA levels. In contrast, neither hypoxia nor overexpression of HIF-1α affected the mRNA levels of PPARα, PPARγ, and muscle carnitine palmitoyltransferase, a known PPARα target gene. These results suggest that hypoxic activation of PGAR expression is likely mediated by HIF-1 but not the PPARα/RXR pathway.