The platelet as a therapeutic target for treating vascular diseases and the role of eicosanoid and synthetic PPARgamma ligands.
The platelet was traditionally thought only to serve as the instigator of thrombus formation, but now is emerging as a pivotal player in cardiovascular disease and diabetes by inciting and maintaining inflammation. Upon activation, platelets synthesize eicosanoids such as thromboxane A2 (TXA2) and PGE2 and release pro-inflammatory mediators including CD40 ligand (CD40L). These mediators activate not only platelets, but also stimulate vascular endothelial cells and leukocytes. These autocrine and paracrine activation processes make platelets an important target for attenuating inflammation. The growing interest and recent discoveries in platelet biology has lead to the search for therapeutic platelet targets. Recently, platelets, although anucleate, were discovered to possess the transcription factor PPARgamma. Treatment with eicosanoid and synthetic PPARgamma ligands blunts platelet release of the bioactive mediators, soluble (s) CD40L and TXA2, in thrombin-activated platelets. PPARgamma ligand treatment may prove useful for dampening unwanted platelet activation and chronic inflammatory diseases such as cardiovascular disease.
O'Brien
Jamie J
JJ
Department of Environmental Medicine and the Lung Biology and Disease Program, University of Rochester, School of Medicine and Dentistry, Box 850, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Ray
Denise M
DM
Spinelli
Sherry L
SL
Blumberg
Neil
N
Taubman
Mark B
MB
Francis
Charles W
CW
Wittlin
Steven D
SD
Phipps
Richard P
RP
D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D015777:Eicosanoids / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology*; D008024:Ligands; D047495:PPAR gamma / Q000187:drug effects* / Q000502:physiology; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D014652:Vascular Diseases / Q000188:drug therapy*
D015777:Eicosanoids; D008024:Ligands; D047495:PPAR gamma; D010975:Platelet Aggregation Inhibitors