Does peroxisome proliferator-activated receptor-γ(PPARγ) protect from hypertension directly through effects in the vasculature?

Peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated transcription factor of the nuclear hormone receptor superfamily. Increasing evidence suggests that PPARγ is involved in the regulation of vascular function and blood pressure in addition to its well recognized role in metabolism. Thiazolidinediones, PPARγ agonists, lower blood pressure and have protective vascular effects through largely unknown mechanisms. In contrast, loss-of-function dominant-negative mutations in human PPARγ cause insulin resistance and severe early onset hypertension. Recent studies using genetically manipulated mouse models have begun to specifically address the importance of PPARγ in the vasculature. In this minireview, evidence for a protective role of PPARγ in the endothelium and vascular smooth muscle, derived largely from studies of genetically manipulated mice, will be discussed.