Peroxisome proliferator-activated receptor gamma and retinoid X receptor transcription factors are released from activated human platelets and shed in microparticles

Peroxisome proliferator-activated receptor gamma (PPAR gamma) and its ligands are important regulators of lipid metabolism, inflammation, and diabetes. We previously demonstrated that anucleate human platelets express the transcription factor PPAR gamma and that PPAR gamma ligands blunt platelet activation. To further understand the nature of PPAR gamma in platelets, we determined the platelet PPARy isoform(s) and investigated the fate of PPAR gamma following platelet activation. Our studies demonstrated that human platelets contain only the PPAR gamma l isoform and after activation with thrombin,TRAP,ADP or collagen PPAR gamma is released from internal stores. PPAR gamma release was blocked by a cytoskeleton inhibitor, Latrunculin A. Platelet-released PPAR gamma was complexed with the retinoid X receptor (RXR) and retained its ability to bind DNA. Interestingly, the released PPAR gamma and RXR were microparticle associated and the released PPAR gamma/RXR complex retained DNA-binding ability. Additionally, a monocytic cell line,THP-1, is capable of internalizing PMPs. Further investigation following treatment of these cells with the PPAR gamma agonist, rosiglitazone and PMPs revealed a possible transcellular mechanism to attenuate THP-1 activation. These new findings are the first to demonstrate transcription factor release from platelets, revealing the complex spectrum of proteins expressed and expelled from platelets, and suggests that platelet PPAR gamma has an undiscovered role in human biology.