Effects of PPARγ on hypertension, atherosclerosis, and chronic kidney disease.
Peroxisome proliferator-activated receptor (PPAR) γ is a nuclear hormone receptor that is trans-activated by its ligands including insulin-sensitizing thiazolidinediones. PPARγ has recently been reported to demonstrate pleiotropic beneficial effects in the vasculatures, independent of its blood glucose-lowering effects. Firstly, PPARγ ligands have been shown to lower blood pressure in both animals and human. The effect may possibly be mediated via the PPARγ-mediated inhibition of the angiotensin (Ang) II type 1 receptor expression as well as Ang II-mediated signaling pathways, which may result in the suppression of the renin-angiotensin system (RAS). Secondly, the progression of atherosclerosis was also prevented by PPARγ ligands in both animals and human. In addition to the PPARγ-mediated suppression of the RAS and the thromboxane A(2) system, protective effects of PPARγ ligands on endothelial function may also be involved. Thirdly, reno-protective effects of PPARγ ligands, especially on reducing urinary albumin, have been observed in both animals and human not only in diabetic nephropathy but also in non-diabetic renal diseases. The reno-protective effects may be mediated, at least in part, via the PPARγ ligand-induced blood pressure-lowering effects, protective effects on endothelial function, and vasodilating effects on the glomerular efferent arterioles. Additionally, anti-cancer effects of PPARγ ligands have recently been reported. Taken together, usefulness and effectiveness of PPARγ ligands on lifestyle related diseases will be increasingly appreciated.
Sugawara
Akira
A
Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine, Sendai, Japan. akiras2i@med.tohoku.ac.jp
Uruno
Akira
A
Kudo
Masataka
M
Matsuda
Ken
K
Yang
Chul Woo
CW
Ito
Sadayoshi
S
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000517:prevention & control; D018450:Disease Progression; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D008024:Ligands; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000502:physiology*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
D000959:Antihypertensive Agents; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D014665:Vasodilator Agents