Effects of PPARγ on hypertension, atherosclerosis, and chronic kidney disease

Endocr J. 2010;57(10):847-52. doi: 10.1507/endocrj.k10e-281. Epub 2010 Sep 28.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / metabolism
  • Diabetic Nephropathies / prevention & control
  • Disease Progression
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Kidney Failure, Chronic / prevention & control
  • Ligands
  • PPAR gamma / agonists*
  • PPAR gamma / genetics
  • PPAR gamma / physiology*
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / metabolism
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use*
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use

Substances

  • Antihypertensive Agents
  • Ligands
  • PPAR gamma
  • Thiazolidinediones
  • Vasodilator Agents