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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3766-3772. Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-08-2712. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-08-2712v1 103/10/3766    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 Yasuda, S. Articles by Koike, T. Search for Related Content PubMed PubMed Citation Articles by Yasuda, S. Articles by Koike, T. Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Nicked 2-glycoprotein I: a marker of cerebral infarct and a novel role in the negative feedback pathway of extrinsic fibrinolysis Shinsuke Yasuda, Tatsuya Atsumi, Masahiro Ieko, Eiji Matsuura, Kazuko Kobayashi, Junko Inagaki, Hisao Kato, Hideyuki Tanaka, Minoru Yamakado, Minoru Akino, Hisatoshi Saitou, Yoshiharu Amasaki, Satoshi Jodo, Olga Amengual, and Takao Koike From the Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan; Department of Cell Chemistry, Institute of Molecular and Cellular Biology, Okayama University Medical School, Okayama, Japan; National Cardiovascular Center Research Institute, Osaka, Japan; Narita R&D Center, Iatron laboratories Inc, Mito, Chiba, Japan; Department of Medicine, Mitsui Memorial Hospital, Tokyo, Japan; Department of Neurosurgery, Azabu Neurosurgical Hospital, Sapporo, Japan. 2-Glycoprotein I (2-GPI) is proteolytically cleaved by plasmin in domain V (nicked 2-GPI), being unable to bind to phospholipids. This cleavage may occur in vivo and elevated plasma levels of nicked 2-GPI were detected in patients with massive plasmin generation and fibrinolysis turnover. In this study, we report higher prevalence of elevated ratio of nicked 2-GPI against total 2-GPI in patients with ischemic stroke (63%) and healthy subjects with lacunar infarct (27%) when compared to healthy subjects with normal findings on magnetic resonance imaging (8%), suggesting that nicked 2-GPI might have a physiologic role beyond that of its parent molecule in patients with thrombosis. Several inhibitors of extrinsic fibrinolysis are known, but a negative feedback regulator has not been yet documented. We demonstrate that nicked 2-GPI binds to Glu-plasminogen with KD of 0.37 x 10–6 M, presumably mediated by the interaction between the fifth domain of nicked 2-GPI and the fifth kringle domain of Glu-plasminogen. Nicked 2-GPI also suppressed plasmin generation up to 70% in the presence of tissue plasminogen activator, plasminogen, and fibrin. Intact 2-GPI lacks these properties. These data suggest that 2-GPI/plasmin-nicked 2-GPI controls extrinsic fibrinolysis via a negative feedback pathway loop. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Nakagawa, S. Yasuda, E. Matsuura, K. Kobayashi, M. Ieko, H. Kataoka, T. Horita, T. Atsumi, and T. Koike Nicked {beta}2-glycoprotein I binds angiostatin 4.5 (plasminogen kringle 1-5) and attenuates its antiangiogenic property Blood, September 17, 2009; 114(12): 2553 - 2559. [Abstract] [Full Text] [PDF] R Forastiero and M Martinuzzo Prothrombotic mechanisms based on the impairment of fibrinolysis in the antiphospholipid syndrome Lupus, October 1, 2008; 17(10): 872 - 877. [Abstract] [PDF] E Cockrell, R. Espinola, and K. McCrae Annexin A2: biology and relevance to the antiphospholipid syndrome Lupus, October 1, 2008; 17(10): 944 - 952. [Abstract] [PDF] T. Sakai, K. Balasubramanian, S. Maiti, J. B. Halder, and A. J. Schroit Plasmin-Cleaved {beta}-2-Glycoprotein 1 Is an Inhibitor of Angiogenesis Am. J. Pathol., November 1, 2007; 171(5): 1659 - 1669. [Abstract] [Full Text] [PDF] B. Giannakopoulos, F. Passam, S. Rahgozar, and S. A. Krilis Current concepts on the pathogenesis of the antiphospholipid syndrome Blood, January 15, 2007; 109(2): 422 - 430. [Abstract] [Full Text] [PDF] L. Anderson Candidate-based proteomics in the search for biomarkers of cardiovascular disease J. Physiol., February 15, 2005; 563(1): 23 - 60. [Abstract] [Full Text] [PDF] T. Shi, B. Giannakopoulos, G. M. Iverson, K. A. Cockerill, M. D. Linnik, and S. A. Krilis Domain V of {beta}2-Glycoprotein I Binds Factor XI/XIa and Is Cleaved at Lys317-Thr318 J. Biol. Chem., January 14, 2005; 280(2): 907 - 912. [Abstract] [Full Text] [PDF]

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