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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2127-2134. Prepublished online as a Blood First Edition Paper on November 26, 2003; DOI 10.1182/blood-2003-04-1133. This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: 2003-04-1133v1 103/6/2127    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 Sim, D. S. Articles by Flaumenhaft, R. Search for Related Content PubMed PubMed Citation Articles by Sim, D. S. Articles by Flaumenhaft, R. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Initial accumulation of platelets during arterial thrombus formation in vivo is inhibited by elevation of basal cAMP levels Derek S. Sim, Glenn Merrill-Skoloff, Barbara C. Furie, Bruce Furie, and Robert Flaumenhaft From the Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Platelet accumulation at sites of vascular injury is the primary event in arterial thrombosis. Initial platelet accrual into thrombi is mediated by interactions of platelet adhesion receptors with ligands on the injured endothelium or in the sub-endothelial matrix. The role of intracellular signals in initial platelet accumulation at sites of endothelial injury, however, is the subject of debate. We have used a newly discovered inhibitor of phosphodiesterase 3A (PDE3A) and the well-characterized PDE3A inhibitor, cilostazol, to modulate 3',5'-cyclic adenosine monophosphate (cAMP) levels in an in vivo model that enables the kinetic analysis of platelet accumulation. These studies demonstrate that elevation of basal cAMP levels results in an overall decline in platelet accumulation at the site of vascular injury. In particular, the initial rate of accumulation of platelets is inhibited by elevation of cAMP. Analysis of the kinetics of individual platelets at injury sites using intravital microscopy demonstrates that cAMP directs the rate at which platelets attach to and detach from thrombi. These studies demonstrate that cAMP in circulating platelets controls attachment to and detachment from sites of arteriolar injury. Thus, the status of the intracellular signaling machinery prior to engagement of platelet receptors influences the rate of platelet accumulation during thrombus formation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. J. Graham, Q. Ren, J. R. Dilks, P. Blair, S. W. Whiteheart, and R. Flaumenhaft Endobrevin/VAMP-8-dependent dense granule release mediates thrombus formation in vivo Blood, July 30, 2009; 114(5): 1083 - 1090. [Abstract] [Full Text] [PDF] D. S. Sim, J. R. Dilks, and R. Flaumenhaft Platelets Possess and Require an Active Protein Palmitoylation Pathway for Agonist-Mediated Activation and In Vivo Thrombus Formation Arterioscler Thromb Vasc Biol, June 1, 2007; 27(6): 1478 - 1485. [Abstract] [Full Text] [PDF] R. Flaumenhaft, E. Tanaka, G. J. Graham, A. M. De Grand, R. G. Laurence, K. Hoshino, R. J. Hajjar, and J. V. Frangioni Localization and Quantification of Platelet-Rich Thrombi in Large Blood Vessels With Near-Infrared Fluorescence Imaging Circulation, January 2, 2007; 115(1): 84 - 93. [Abstract] [Full Text] [PDF] C. Dubois, L. Panicot-Dubois, G. Merrill-Skoloff, B. Furie, and B. C. Furie Glycoprotein VI-dependent and -independent pathways of thrombus formation in vivo Blood, May 15, 2006; 107(10): 3902 - 3906. [Abstract] [Full Text] [PDF] S. Falati, S. Patil, P. L. Gross, M. Stapleton, G. Merrill-Skoloff, N. E. Barrett, K. L. Pixton, H. Weiler, B. Cooley, D. K. Newman, et al. Platelet PECAM-1 inhibits thrombus formation in vivo Blood, January 15, 2006; 107(2): 535 - 541. [Abstract] [Full Text] [PDF]

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