The platelet as a therapeutic target for treating vascular diseases and the role of eicosanoid and synthetic PPARγ ligands

• Published in: Prostaglandins & other lipid mediators Vol. 82; no. 1; pp. 68 - 76
• Main Authors: O’Brien, Jamie J., Ray, Denise M., Spinelli, Sherry L., Blumberg, Neil, Taubman, Mark B., Francis, Charles W., Wittlin, Steven D., Phipps, Richard P.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 2007
• Subjects: Cardiovascular disease; CD40 ligand; Diabetes; Platelet; PPARγ; Thromboxane; Cardiovascular disease; Platelet; Diabetes; Thromboxane; CD40 ligand; PPARγ
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2006.05.018

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 A 2 (TXA 2) and PGE 2 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 PPARγ. Treatment with eicosanoid and synthetic PPARγ ligands blunts platelet release of the bioactive mediators, soluble (s) CD40L and TXA 2, in thrombin-activated platelets. PPARγ ligand treatment may prove useful for dampening unwanted platelet activation and chronic inflammatory diseases such as cardiovascular disease.