Platelets as a novel target for PPARgamma ligands : implications for inflammation, diabetes, and cardiovascular disease.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is an important transcription factor for lipid and glucose metabolism. Currently, the PPARgamma ligands rosiglitazone and pioglitazone are used for the treatment of type 2 diabetes mellitus because they are potent insulin sensitizers. Recently, PPARgamma has emerged as an important anti-inflammatory factor. Platelets, anucleate cells involved in hemostasis, have also been implicated as key contributors to inflammation, because they produce many pro-inflammatory and pro-atherogenic mediators when activated. Surprisingly, it was discovered recently that platelets contain PPARgamma and that PPARgamma ligands, both natural and synthetic, inhibit platelet activation and release of bioactive mediators. In particular, release of soluble CD40 ligand (sCD40L) and thromboxane (TXA(2)) was inhibited by PPARgamma ligands in thrombin-activated platelets. CD40L signaling induces pro-inflammatory processes in many cell types, and increased blood levels of sCD40L are closely associated with inflammation, diabetes, and cardiovascular disease. Targeting platelet PPARgamma will, therefore, be an important treatment strategy for the attenuation of chronic inflammatory processes and prevention of thrombus formation.
Ray
Denise M
DM
Department of Environmental Medicine and the Lung Biology and Disease Program, University of Rochester, Rochester, New York 14642, USA.
Spinelli
Sherry L
SL
O'Brien
Jamie J
JJ
Blumberg
Neil
N
Phipps
Richard P
RP
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D016503:Drug Delivery Systems; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D008024:Ligands; D008954:Models, Biological; D047495:PPAR gamma / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects
D008024:Ligands; D047495:PPAR gamma