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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3783-3788. Prepublished online as a Blood First Edition Paper on January 29, 2004; DOI 10.1182/blood-2003-12-4240. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4240v1 103/10/3783    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 Lee, K. N. Articles by McKee, P. A. Search for Related Content PubMed PubMed Citation Articles by Lee, K. N. Articles by McKee, P. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A novel plasma proteinase potentiates 2-antiplasmin inhibition of fibrin digestion Kyung N. Lee, Kenneth W. Jackson, Victoria J. Christiansen, Keun H. Chung, and Patrick A. McKee From the William K. Warren Medical Research Center and the Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK. Human 2-antiplasmin (2AP), also known as 2-plasmin inhibitor, is the major inhibitor of the proteolytic enzyme plasmin that digests fibrin. There are 2 N-terminal forms of 2AP that circulate in human plasma: a 464-residue protein with Met as the N-terminus, Met-2AP, and a 452-residue version with Asn as the N-terminus, Asn-2AP. We have discovered and purified a proteinase from human plasma that cleaves the Pro12-Asn13 bond of Met-2AP to yield Asn-2AP and have named it antiplasmin-cleaving enzyme (APCE). APCE is similar in primary structure and catalytic properties to membrane-bound fibroblast activation protein/seprase for which a physiologic substrate has not been clearly defined. We found that Asn-2AP becomes cross-linked to fibrin by activated factor XIII approximately 13 times faster than native Met-2AP during clot formation and that clot lysis rates are slowed in direct proportion to the ratio of Asn-2AP to Met-2AP in human plasma. We conclude that APCE cleaves Met-2AP to the derivative Asn-2AP, which is more efficiently incorporated into fibrin and consequently makes it strikingly resistant to plasmin digestion. APCE may represent a new target for pharmacologic inhibition, since less generation and incorporation of Asn-2AP could result in a more rapid removal of fibrin by plasmin during atherogenesis, thrombosis, and inflammatory states. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A snip enhances 2-antiplasmin Nuala A. Booth and Louise Thomas Blood 2004 103: 3612. [Full Text] [PDF] This article has been cited by other articles: V. J. Christiansen, K. W. Jackson, K. N. Lee, and P. A. McKee The effect of a single nucleotide polymorphism on human {alpha}2-antiplasmin activity Blood, June 15, 2007; 109(12): 5286 - 5292. [Abstract] [Full Text] [PDF] C. Y. Edosada, C. Quan, C. Wiesmann, T. Tran, D. Sutherlin, M. Reynolds, J. M. Elliott, H. Raab, W. Fairbrother, and B. B. Wolf Selective Inhibition of Fibroblast Activation Protein Protease Based on Dipeptide Substrate Specificity J. Biol. Chem., March 17, 2006; 281(11): 7437 - 7444. [Abstract] [Full Text] [PDF] K. N. Lee, K. W. Jackson, V. J. Christiansen, C. S. Lee, J.-G. Chun, and P. A. McKee Antiplasmin-cleaving enzyme is a soluble form of fibroblast activation protein Blood, February 15, 2006; 107(4): 1397 - 1404. [Abstract] [Full Text] [PDF]

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