Vascular effects of prostacyclin: does activation of PPARδ play a role?

Prostacyclin (PGI2) is a potent vasodilator that exerts multiple vasoprotective effects in the cardiovascular system. The effects of PGI2 are mediated by activation of the cell membrane G-protein-coupled PGI2 receptor (IP receptor). More recently, however, it has been suggested that PGI2 might also serve as an endogenous ligand and activator of nuclear peroxisome proliferator-activated receptorδ (PPARδ). Consistent with this concept, studies designed to define pharmacological properties of stable PGI2 analogs revealed that beneficial effects of these compounds appear to be mediated, in part, by activation of PPARδ. This review discusses emerging evidence regarding the contribution of PPARδ activation to vasoprotective and regenerative functions of PGI2 and stable analogs of PGI2.