PPAR gamma Regulation in Hypertension and Metabolic Syndrome

摘要

Dysregulation of peroxisome proliferator-activated receptor gamma (PPAR gamma) activity leads to significant alterations in cardiovascular and metabolic regulation. This is most keenly observed by the metabolic syndrome-like phenotypes exhibited by patients carrying mutations in PPAR gamma. We will summarize recent findings regarding mechanisms of PPAR gamma regulation in the cardiovascular and nervous systems focusing largely on PPAR gamma in the smooth muscle, endothelium, and brain. Canonically, PPAR gamma exerts its effects by regulating the expression of target genes in these cells, and we will discuss mechanisms by which PPAR gamma targets in the vasculature regulate cardiovascular function. We will also discuss emerging evidence that PPAR gamma in the brain is a mediator of appetite and obesity. Finally, we will briefly review how novel PPAR gamma activators control posttranslational modifications of PPAR gamma and their prospects to offer new therapeutic options for treatment of metabolic diseases without the adverse side effects of thiazolidinediones which strongly activate transcriptional activity of PPAR gamma.