title: PPARγ agonist beyond glucose lowering effect.
abstract: The nuclear hormone receptor PPARγ 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. PPARγ 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. PPARγ agonists also inhibit the progression of atherosclerosis in animals and humans, possibly through a pathway involving the suppression of RAAS and the thromboxane A₂ system, as well as the protection of endothelial function. Moreover, PPARγ-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 PPARγ agonists to lower blood pressure, protect endothelial function, and cause vasodilation of the glomerular efferent arterioles. Additionally, anti-neoplastic effects of PPARγ agonists have recently been described. Based on the multiple therapeutic actions of PPARγ agonists, they will no doubt lead to novel approaches in the treatment of lifestyle-related and other diseases.
authors: Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine, Sendai, Japan. akiras2i@med.tohoku.ac.jp
authors: Akira
authors: A
authors: Sugawara
authors: Akira
authors: A
authors: Uruno
authors: Masataka
authors: M
authors: Kudo
authors: Ken
authors: K
authors: Matsuda
authors: Chul Woo
authors: CW
authors: Yang
authors: Sadayoshi
authors: S
authors: Ito
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007674:Kidney Diseases / Q000209:etiology; D047495:PPAR gamma / Q000819:agonists*; D048068:PPAR-beta / Q000819:agonists
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D048068:PPAR-beta