• Ferhana Y Ali, Matthew G Hall, Béatrice Desvergne, Timothy D Warner, and Jane A Mitchell.
• Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, London, UK.
• Arterioscler. Thromb. Vasc. Biol. 2009 Nov 1; 29 (11): 1871-3.

ObjectivePeroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) is a nuclear receptor found in platelets. PPARbeta/delta agonists acutely inhibit platelet function within a few minutes of addition. As platelets are anucleated, the effects of PPARbeta/delta agonists on platelets must be nongenomic. Currently, the particular role of PPARbeta/delta receptors and their intracellular signaling pathways in platelets are not known.Methods And ResultsWe have used mice lacking PPARbeta/delta (PPARbeta/delta(-/-)) to show the effects of the PPARbeta/delta agonist GW501516 on platelet adhesion and cAMP levels are mediated specifically by PPARbeta/delta, however GW501516 had no PPARbeta/delta-specific effect on platelet aggregation. Studies in human platelets showed that PKCalpha, which can mediate platelet activation, was bound and repressed by PPARbeta/delta after platelets were treated with GW501516.ConclusionsThese data provide evidence of a novel mechanism by which PPAR receptors influence platelet activity and thereby thrombotic risk.

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