SEARCH:   Advanced

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 (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 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. Social Bookmarking                   What's this? Submitted August 7, 2003 Accepted January 5, 2004 Nicked beta2-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 Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 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 Azabu Neurosurgical Hospital, Department of Neurosurgery, Sapporo, Japan * Corresponding author; email: at3tat{at}med.hokudai.ac.jp. 2-glycoprotein I (2GPI) is proteolytically cleaved by plasmin in domain V (nicked 2GPI), being unable to bind to phospholipids. This cleavage may occur in vivo and elevated plasma levels of nicked 2GPI were detected in patients with massive plasmin generation and fibrinolysis turnover. In this study, we reported higher prevalence of elevated ratio of nicked 2GPI against total 2GPI in patients with ischemic stroke (63%) and healthy subjects with lacunar infarct (27%) when compared to healthy subjects with normal MRI findings (8%), suggesting that nicked 2GPI might have a physiological 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 demonstrated that nicked 2GPI binds to Glu-plasminogen with KD of 0.37 x 10-6 M, presumably mediated by the interaction between the fifth domain of nicked 2GPI and the fifth kringle domain of Glu-plasminogen. Nicked 2GPI also suppressed plasmin generation up to 70% in the presence of tissue plasminogen activator, plasminogen, and fibrin. Intact 2GPI lacks these properties. These data suggest that 2GPI/plasmin-nicked 2GPI control 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]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020