Pleiotropic Effects of Peroxisome Proliferator-Activated Receptor γ and δ in Vascular Diseases

Peroxisome proliferator-activated receptors gamma (PPAR gamma) and delta (PPAR delta) are nuclear receptors that have significant physiological effects on glucose and lipid metabolism. Experimental studies in animal models of metabolic disease have demonstrated their effects on improving lipid profile, insulin sensitivity, and reducing inflammatory responses. PPAR gamma and -delta are also expressed in the vasculature and their beneficial effects have been examined in various cardiovascular disease models such as atherosclerosis, hypertension, diabetic vascular complications, etc. using pharmacological ligands or genetic tools including viral vectors and transgenic mice. These studies suggest that PPAR gamma and delta are antiinflammatory, antiatherogenic, antioxidant, and antifibrotic against vascular diseases. Several signaling pathways, effector molecules, as well as coactivators/repressors have been identified as responsible for the protective effects of PPAR gamma and -delta in the vasculature. We discuss the pleiotropic effect of PPAR gamma and 6 in vascular dysfunction, including atherosclerosis, hypertension, vascular remodeling, vascular injury, and diabetic vasculopathy, in various animal models, and the major underlying mechanisms. We also compare the phenotypes-of several endothelial cell/vascular smooth muscle-specific PPAR gamma and -delta knockout and overexpressing transgenic mice in various disease models, and the implications underlying the functional importance of vascular PPAR gamma and delta in regulating whole-body homeostasis.