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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1943-1950. Prepublished online as a Blood First Edition Paper on November 17, 2005; DOI 10.1182/blood-2005-07-2972. This Article Full Text (PDF) Supplemental Videos All Versions of this Article: 2005-07-2972v1 107/5/1943    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 Donadelli, R. Articles by Ruggeri, Z. M Search for Related Content PubMed PubMed Citation Articles by Donadelli, R. Articles by Ruggeri, Z. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 25, 2005 Accepted October 25, 2005 Size regulation of von Willebrand factor-mediated platelet thrombi by ADAMTS-13 in flowing blood Roberta Donadelli, Jennifer N Orje, Cristina Capoferri, Giuseppe Remuzzi, and Zaverio M Ruggeri* Roon Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA; Mario Negri Institute for Pharmacological Research, Bergamo, Italy Roon Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA Mario Negri Institute for Pharmacological Research, Bergamo, Italy * Corresponding author; email: ruggeri{at}scripps.edu. The metalloproteinase, ADAMTS-13, regulates the size of released von Willebrand factor (VWF) multimers bound to endothelial cells, but it is unknown whether it can cleave plasma VWF during thrombogenesis. To address this issue, we perfused blood over immobilized VWF and used videomicroscopy to visualize an activation-independent platelet aggregation process mediated by soluble VWF at shear rates >10,000 s-1. At normal Ca2+ concentration, platelets formed rolling as well as surface-attached clusters that grew larger during the first 5 min but then lost >70% of their mass by 10 min. In contrast, platelet clusters were stable in size when metal ions were chelated, anti-ADAMTS-13 IgG were added, or washed blood cells were perfused with purified VWF but no plasma. In the latter case, addition of recombinant ADAMTS-13 reduced platelet cluster size by >70%. Incubating ADAMTS-13 with VWF before perfusion did not prevent the initial platelet clustering, indicating that the enzyme may act on platelet-bound VWF under shear stress. At the concentrations tested, ADAMTS-13 had no effect on platelet aggregates formed upon blood perfusion over collagen fibrils. ADAMTS-13, therefore, may regulate thrombus size preferentially when the cohesion between platelets depends on VWF binding induced by pathologically elevated shear stress. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Banno, A. K. Chauhan, K. Kokame, J. Yang, S. Miyata, D. D. Wagner, and T. Miyata The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation Blood, May 21, 2009; 113(21): 5323 - 5329. [Abstract] [Full Text] [PDF] M.-C. Chung, T. G. Popova, S. C. Jorgensen, L. Dong, V. Chandhoke, C. L. Bailey, and S. G. 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Res., June 22, 2007; 100(12): 1673 - 1685. [Abstract] [Full Text] [PDF] S. W. Schneider, S. Nuschele, A. Wixforth, C. Gorzelanny, A. Alexander-Katz, R. R. Netz, and M. F. Schneider Shear-induced unfolding triggers adhesion of von Willebrand factor fibers PNAS, May 8, 2007; 104(19): 7899 - 7903. [Abstract] [Full Text] [PDF] Z. M. Ruggeri, J. N. Orje, R. Habermann, A. B. Federici, and A. J. Reininger Activation-independent platelet adhesion and aggregation under elevated shear stress Blood, September 15, 2006; 108(6): 1903 - 1910. [Abstract] [Full Text] [PDF]

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