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

Prostacyclin (PGI(2)) is a potent vasodilator that exerts multiple vasoprotective effects in the cardiovascular system. The effects of PGI(2) are mediated by activation of the cell membrane G-protein-coupled PGI(2) receptor (IP receptor). More recently, however, it has been suggested that PGI(2) might also serve as an endogenous ligand and activator of nuclear peroxisome proliferator-activated receptors (PPAR delta). Consistent with this concept, studies designed to define pharmacological properties of stable PGI(2) analogs revealed that beneficial effects of these compounds appear to be mediated, in part, by activation of PPAR delta. This review discusses emerging evidence regarding the contribution of PPAR delta activation to vasoprotective and regenerative functions of PGI(2) and stable analogs of PGI(2).