PPAR / Agonists Modulate Platelet Function via a Mechanism Involving PPAR Receptors and Specific Association/Repression of PKC

Objectives—Peroxisome proliferator-activated receptor / (PPAR / ) is a nuclear receptor found in platelets. PPAR / agonists acutely inhibit platelet function within a few minutes of addition. As platelets are anucleated, the effects of PPAR / agonists on platelets must be nongenomic. Currently, the particular role of PPAR / receptors and their intracellular signaling pathways in platelets are not known. Methods and Results—We have used mice lacking PPAR / (PPAR / / ) to show the effects of the PPAR / agonist GW501516 on platelet adhesion and cAMP levels are mediated specifically by PPAR / , however GW501516 had no PPAR / -specific effect on platelet aggregation. Studies in human platelets showed that PKC , which can mediate platelet activation, was bound and repressed by PPAR / after platelets were treated with GW501516. Conclusions—These data provide evidence of a novel mechanism by which PPAR receptors influence platelet activity and thereby thrombotic risk. (Arterioscler Thromb Vasc Biol. 2009;29:00-00.)