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Blood, 8 October 2009, Vol. 114, No. 15, pp. 3329-3334. Prepublished online as a Blood First Edition Paper on August 17, 2009; DOI 10.1182/blood-2009-03-213264. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-03-213264v1 114/15/3329    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 CrossRef Google Scholar Articles by Zhao, B.-Q. Articles by Wagner, D. D. PubMed PubMed Citation Articles by Zhao, B.-Q. Articles by Wagner, D. D. Related Collections Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS von Willebrand factor–cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke Bing-Qiao Zhao13, Anil K. Chauhan13, Matthias Canault13, Ian S. Patten1,2, Janie J. Yang1,2, Michael Dockal4, Friedrich Scheiflinger4, and Denisa D. Wagner13 1 Immune Disease Institute, Boston, MA; 2 Program in Cellular and Molecular Medicine, Children's Hospital, Boston, MA; 3 Department of Pathology, Harvard Medical School, Boston, MA; and 4 Baxter Bioscience, Vienna, Austria Stroke is a leading cause of death and disability. The only therapy available is recombinant tissue plasminogen activator, but side effects limit its use. Platelets play a crucial role during stroke, and the inflammatory reaction promotes neurodegeneration. von Willebrand factor (VWF), an adhesion molecule for platelets, is elevated in patients with acute stroke. The activity of VWF is modulated by ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) that cleaves VWF to smaller less-active forms. We recently documented that ADAMTS13 negatively regulates both thrombosis and inflammation. We report that deficiency or reduction of VWF reduces infarct volume up to 2-fold after focal cerebral ischemia in mice, thus showing the importance of VWF in stroke injury. In contrast, ADAMTS13 deficiency results in larger infarctions, but only in mice that have VWF. Importantly, infusion of a high dose of recombinant human ADAMTS13 into a wild-type mouse immediately before reperfusion reduces infarct volume and improves functional outcome without producing cerebral hemorrhage. Furthermore, recombinant ADAMTS13 did not enhance bleeding in a hemorrhagic stroke model. Our findings show the importance of VWF in regulating infarction and suggest that recombinant ADAMTS13 could be considered as a new therapeutic agent for prevention and/or treatment of stroke. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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