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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1257-1265. Prepublished online as a Blood First Edition Paper on November 7, 2007; DOI 10.1182/blood-2007-05-092684. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-092684v1 111/3/1257    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 Jobe, S. M. Articles by Di Paola, J. Search for Related Content PubMed PubMed Citation Articles by Jobe, S. M. Articles by Di Paola, J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis Shawn M. Jobe1, Katina M. Wilson2, Lorie Leo2, Alejandro Raimondi1, Jeffery D. Molkentin3, Steven R. Lentz2,4, and Jorge Di Paola1 Departments of1 Pediatrics and 2 Internal Medicine, University of Iowa Carver College of Medicine, Iowa City; 3 Department of Pediatrics, University of Cincinnati, OH; and 4 Veteran Affairs Medical Center, Iowa City, IA Many of the cellular responses that occur in activated platelets resemble events that take place following activation of cell-death pathways in nucleated cells. We tested the hypothesis that formation of the mitochondrial permeability transition pore (MPTP), a key signaling event during cell death, also plays a critical role in platelet activation. Stimulation of murine platelets with thrombin plus the glycoprotein VI agonist convulxin resulted in a rapid loss of mitochondrial transmembrane potential (m) in a subpopulation of activated platelets. In the absence of cyclophilin D (CypD), an essential regulator of MPTP formation, murine platelet activation responses were altered. CypD-deficient platelets exhibited defects in phosphatidylserine externalization, high-level surface fibrinogen retention, membrane vesiculation, and procoagulant activity. Also, in CypD-deficient platelet-rich plasma, clot retraction was altered. Stimulation with thrombin plus H2O2, a known activator of MPTP formation, also increased high-level surface fibrinogen retention, phosphatidylserine externalization, and platelet procoagulant activity in a CypD-dependent manner. In a model of carotid artery photochemical injury, thrombosis was markedly accelerated in CypD-deficient mice. These results implicate CypD and the MPTP as critical regulators of platelet activation and suggest a novel CypD-dependent negative-feedback mechanism regulating arterial thrombosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Mitochondria push platelets past their prime Fernando A. Bozza and Andrew S. Weyrich Blood 2008 111: 2496-2497. [Full Text] [PDF] This article has been cited by other articles: R. Chen, X. Chen, R. G. Salomon, and T. M. McIntyre Platelet Activation by Low Concentrations of Intact Oxidized LDL Particles Involves the PAF Receptor Arterioscler. Thromb. Vasc. Biol., March 1, 2009; 29(3): 363 - 371. [Abstract] [Full Text] [PDF]

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