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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 10, 2004 Accepted April 26, 2004 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* Biochemistry, Hacettepe University, Ankara, Turkey; Environmental Medicine, Microbiology and Immunology, and the Lung Biology and Disease Program, University of Rochester, Rochester, NY, USA Environmental Medicine, Microbiology and Immunology, and the Lung Biology and Disease Program, University of Rochester, Rochester, NY, USA Pathology and Laboratory Medicine, University of Rochester, Rochester, NY, USA Medicine, Hematology/Oncology Unit, University of Rochester, Rochester, NY, USA * Corresponding author; email: richard_phipps{at}urmc.rochester.edu. 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 not only essential for clotting, but have an emerging role in inflammation in part due to their release or production of the pro-inflammatory and pro-atherogenic mediators CD40 ligand (L) and thromboxanes (TX). 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 TXB2. 15d-PGJ2 also inhibited platelet aggregation and ATP release. Our results show that human platelets express PPAR and that PPAR agonists such as the thiazolidinedione class of anti-diabetic 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: J. J. Bernard, K. E. Seweryniak, A. D. Koniski, S. L. Spinelli, N. Blumberg, C. W. Francis, M. B. Taubman, J. Palis, and R. P. Phipps Foxp3 Regulates Megakaryopoiesis and Platelet Function Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1874 - 1882. [Abstract] [Full Text] [PDF] R. P. Phipps and N. Blumberg Statin Islands and PPAR Ligands in Platelets Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 620 - 621. [Full Text] [PDF] F. Y. Ali, P. C.J. Armstrong, A.-R. A. Dhanji, A. T. Tucker, M. J. Paul-Clark, J. A. Mitchell, and T. D. Warner Antiplatelet Actions of Statins and Fibrates Are Mediated by PPARs Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 706 - 711. [Abstract] [Full Text] [PDF] 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. J. O'Brien, S. L. Spinelli, J. Tober, N. Blumberg, C. W. Francis, M. B. Taubman, J. Palis, K. E. Seweryniak, J. M. Gertz, and R. P. Phipps 15-deoxy-{Delta}12,14-PGJ2 enhances platelet production from megakaryocytes Blood, November 15, 2008; 112(10): 4051 - 4060. [Abstract] [Full Text] [PDF] J. A. Mitchell, F. Ali, L. Bailey, L. 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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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