Affiliation:
1. From the Department of Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey; the Departments of Environmental Medicine, Pathology and Laboratory Medicine, and Microbiology and Immunology, and the Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry; and the Hematology/Oncology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY.
Abstract
AbstractPeroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor important in lipid metabolism, diabetes, and inflammation. We evaluated whether human platelets and megakaryocytes express PPARγ and whether PPARγ agonists influence platelet release of bioactive mediators. Although PPARγ is mainly considered a nuclear receptor, we show that enucleate platelets highly express PPARγ protein as shown by Western blotting, flow cytometry, and immunocytochemistry. Meg-01 megakaryocyte cells and human bone marrow megakaryocytes also express PPARγ. Platelet and Meg-01 PPARγ bound the PPARγ DNA consensus sequence, and this was enhanced by PPARγ agonists. Platelets are essential not only for clotting, but have an emerging role in inflammation in part due to their release or production of the proinflammatory and proatherogenic mediators CD40 ligand (CD40L) and thromboxanes (TXs). Platelet incubation with a natural PPARγ agonist, 15d-PGJ2, or with a potent synthetic PPARγ ligand, rosiglitazone, prevented thrombin-induced CD40L surface expression and release of CD40L and thromboxane B2 (TXB2). 15d-PGJ2 also inhibited platelet aggregation and adenosine triphosphate (ATP) release. Our results show that human platelets express PPARγ and that PPARγ agonists such as the thiazolidinedione class of antidiabetic drugs have a new target cell, the platelet. This may represent a novel mechanism for treatment of inflammation, thrombosis, and vascular disease in high-risk patients.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
175 articles.
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