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Vascular effects of prostacyclin: does activation of PPARδ play a role?
Katusic ZS, Santhanam AV, He T.
SourceDepartments of Anesthesiology, Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA.
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 receptorδ (PPARδ). 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 PPARδ. This review discusses emerging evidence regarding the contribution of PPARδ activation to vasoprotective and regenerative functions of PGI(2) and stable analogs of PGI(2).