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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1361-1368. Prepublished online as a Blood First Edition Paper on May 6, 2004; DOI 10.1182/blood-2004-03-0926. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0926v1 104/5/1361    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Akbiyik, F. Articles by Phipps, R. P. Search for Related Content PubMed PubMed Citation Articles by Akbiyik, F. Articles by Phipps, R. P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Human bone marrow megakaryocytes and platelets express PPAR, and PPAR agonists blunt platelet release of CD40 ligand and thromboxanes Filiz Akbiyik, Denise M. Ray, Kelly F. Gettings, Neil Blumberg, Charles W. Francis, and Richard P. Phipps 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. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor important in lipid metabolism, diabetes, and inflammation. We evaluated whether human platelets and megakaryocytes express PPAR and whether PPAR agonists influence platelet release of bioactive mediators. Although PPAR is mainly considered a nuclear receptor, we show that enucleate platelets highly express PPAR protein as shown by Western blotting, flow cytometry, and immunocytochemistry. Meg-01 megakaryocyte cells and human bone marrow megakaryocytes also express PPAR. Platelet and Meg-01 PPAR bound the PPAR DNA consensus sequence, and this was enhanced by PPAR 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 PPAR agonist, 15d-PGJ2, or with a potent synthetic PPAR 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 PPAR and that PPAR 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. A. Khorana, C. W. Francis, N. Blumberg, E. Culakova, M. A. Refaai, and G. H. Lyman Blood Transfusions, Thrombosis, and Mortality in Hospitalized Patients With Cancer Arch Intern Med, November 24, 2008; 168(21): 2377 - 2381. [Abstract] [Full Text] [PDF] J. A. 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Nuutila Rosiglitazone Treatment Increases Subcutaneous Adipose Tissue Glucose Uptake in Parallel with Perfusion in Patients with Type 2 Diabetes: A Double-Blind, Randomized Study with Metformin J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6523 - 6528. [Abstract] [Full Text] [PDF] C. Digman, A. K. Klein, and A. G. Pittas Leukopenia and Thrombocytopenia Caused by Thiazolidinediones Ann Intern Med, September 20, 2005; 143(6): 465 - 466. [Full Text] [PDF]

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