15-deoxy-delta12,14-PGJ2 enhances platelet production from megakaryocytes.

Thrombocytopenia is a critical problem that occurs in many hematologic diseases, as well as after cancer therapy and radiation exposure. Platelet transfusion is the most commonly used therapy but has limitations of alloimmunization, availability, and expense. Thus, the development of safe, small, molecules to enhance platelet production would be advantageous for the treatment of thrombocytopenia.

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 (PPARgamma) and its ligands are important regulators of lipid metabolism, inflammation, and diabetes. We previously demonstrated that anucleate human platelets express the transcription factor PPARgamma and that PPARgamma ligands blunt platelet activation. To further understand the nature of PPARgamma in platelets, we determined the platelet PPARgamma isoform(s) and investigated the fate of PPARgamma following platelet activation.

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.

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.