PPARγ and RhoBTB1 in hypertension

Purpose of review This review provides an up-to-date understanding of how peroxisome proliferator activated receptor gamma (PPAR gamma) exerts its cardioprotective effect in the vasculature through its activation of novel PPAR gamma target genes in endothelium and vascular smooth muscle. Recent findings In vascular endothelial cells, PPAR gamma plays a protective role by increasing nitric oxide bioavailability and preventing oxidative stress. RBP7 is a PPAR gamma target gene enriched in vascular endothelial cells, which is likely to form a positive feedback loop with PPAR gamma. In vascular smooth muscle cells, PPAR gamma antagonizes the renin-angiotensin system, maintains vascular integrity, suppresses vasoconstriction, and promotes vasodilation through distinct pathways. Rho-related BTB domain containing protein 1 (RhoBTB1) is a novel PPAR gamma gene target in vascular smooth muscle cells that mediates the protective effect of PPAR gamma by serving as a substrate adaptor between the Cullin-3 RING ubiquitin ligase and phosphodiesterase 5, thus restraining its activity through ubiquitination and proteasomal degradation. In the vasculature, PPAR gamma exerts its cardioprotective effect through its transcriptional activity in endothelium and vascular smooth muscle. From the understanding of PPAR gamma's transcription targets in those pathways, novel hypertension therapy target(s) will emerge.