Molecular mechanisms regulating vascular tone by peroxisome proliferator activated receptor gamma

This review summarizes recent findings on the regulation of vascular tone by the nuclear receptor transcription factor, peroxisome proliferator activated receptor (PPAR) γ. Much of the recent work utilizes genetic tools to interrogate the significance of PPARγ in endothelial and smooth muscle cells and novel PPARγ target genes have been identified.

Endothelial PPARγ prevents inflammation and oxidative stress, while promoting vasodilation by controlling the regulation of NADPH oxidase, catalase and superoxide dismutase gene expression. Moreover, the protective functions of endothelial PPARγ appear more prominent during disease conditions. Novel findings also suggest a role for endothelial PPARγ as a mediator of whole body metabolism. In smooth muscle cells, PPARγ regulates vascular tone by targeting genes involved with contraction and relaxation signaling cascades, some of which is via transcriptional activation, and some through novel mechanisms regulating protein turnover. Furthermore, aberrant changes in renin-angiotensin system components and exacerbated responses to angiotensin II induced vascular dysfunction are observed when PPARγ function is lost in smooth muscle cells.

With these recent advances based partially on lessons from patients with PPARγ mutants, we conclude that vascular PPARγ is protective and plays an important role in the regulation of vascular tone.