$PPAR{\gamma}$ Agonist Beyond Glucose Lowering Effect

The nuclear hormone receptor $PPAR{\gamma}$ is activated by several agonists, including members of the thiazolidinedione group of insulin sensitizers. Pleiotropic beneficial effects of these agonists, independent of their blood glucose-lowering effects, have recently been demonstrated in the vasculature. $PPAR{\gamma}$ agonists have been shown to lower blood pressure in animals and humans, perhaps by suppressing the renin-angiotensin (Ang)-aldosterone system (RAAS), including the inhibition of Ang II type 1 receptor expression, Ang-II-mediated signaling pathways, and Ang-II-induced adrenal aldosterone synthesis/secretion. $PPAR{\gamma}$ agonists also inhibit the progression of atherosclerosis in animals and humans, possibly through a pathway involving the suppression of RAAS and the thromboxane $A_2$ system, as well as the protection of endothelial function. Moreover, $PPAR{\gamma}$-agonist-mediated renal protection, especially the reduction of albuminuria, has been observed in diabetic nephropathy, including animal models of the disease, and in non-diabetic renal dysfunction. The renal protective activities may reflect, at least in part, the ability of $PPAR{\gamma}$ agonists to lower blood pressure, protect endothelial function, and cause vasodilation of the glomerular efferent arterioles. Additionally, anti-neoplastic effects of $PPAR{\gamma}$ agonists have recently been described. Based on the multiple therapeutic actions of $PPAR{\gamma}$ agonists, they will no doubt lead to novel approaches in the treatment of lifestyle-related and other diseases.