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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3217-3223. Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-02-0378. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-02-0378v1 102/9/3217    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 Jurasz, P. Articles by Radomski, M. W. Search for Related Content PubMed PubMed Citation Articles by Jurasz, P. Articles by Radomski, M. W. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Generation and role of angiostatin in human platelets Paul Jurasz, David Alonso, Susana Castro-Blanco, Ferid Murad, and Marek W. Radomski From the Department of Pharmacology, University of Alberta, Edmonton, Canada; Department of Integrative Biology and Pharmacology and Institute of Molecular Medicine for the Prevention of Human Disease, University of Texas-Houston; and Department of Neuroanatomy and Cell Biology, Cajal Institute, Spanish Science Research Council (CSIC), Madrid, Spain. Platelets regulate new blood vessel growth, because they contain a number of angiogenesis promoters and inhibitors. Additionally, platelets contain matrix metalloproteinases (MMPs), which when released mediate platelet adhesion and aggregation, and plasminogen, a fibrinolytic system enzyme that serves to limit blood clot formation. Enzymatic cleavage of plasminogen by MMPs generates angiostatin, an angiogenesis inhibitor. Therefore, we examined whether platelets generate angiostatin during aggregation in vitro. Platelets were isolated from healthy human donors and then aggregated with collagen, thrombin, or HT-1080 fibrosarcoma cells. Angiostatin was detected by Western blot analysis in the platelet releasates of all blood donors irrespective of the aggregating agent used. Platelet pellet homogenates showed the presence of angiostatin in all donors, which was released upon aggregation. Furthermore, platelet-derived angiostatin was isolated and purified by lysine-Sepharose affinity chromatography from collagen-aggregated platelet releasates. Bioassay of platelet-derived angiostatin showed that it inhibited the formation of capillary structures by human umbilical vein endothelial cells (HUV-EC-Cs) in an in vitro angiogenesis model. Inhibition of angiostatin in platelet releasates promoted the formation of capillary structures by HUV-EC-Cs. We conclude that healthy human platelets contain angiostatin, which is released in active form during platelet aggregation, and platelet-derived angiostatin has the capacity to inhibit angiogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Brill, H. Elinav, and D. Varon Differential role of platelet granular mediators in angiogenesis Cardiovasc Res, August 1, 2004; 63(2): 226 - 235. [Abstract] [Full Text] [PDF]

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