NDLI: Comparison between the clot-protecting activity of a mutant plasminogen activator inhibitor-1 with a very long half-life and 6-aminocaproic acid

Content Provider	PubMed Central
Author	Kindell, Daniel Glenn Keck, Rick Wayne Jankun, Jerzy
Copyright Year	2015
Abstract	Plasminogen activator inhibitor (PAI)-1 is a serpin glycoprotein that can stabilize blood clots by inhibiting fibrinolysis. However, wild-type PAI-1 has the disadvantage of a short half-life of ∼2 h. A very long half-life (VLHL) PAI-1 mutant was developed previously with an active-form half-life of >700 h, making it a possible candidate for use in hemorrhagic therapy. Current treatments for mitigating hemorrhage, other than inducers of blood clotting, are limited to lysine analog antifibrinolytics, including 6-aminocaproic acid and tranexamic acid. VLHL PAI-1 has been previously demonstrated to limit bleeding; however, the efficacy of this protein compared with lysine analog antifibrinolytics has not been investigated. The aim of the current study was to compare the clot stabilizing properties of the novel antifibrinolytic VLHL PAI-1 with those of 6-aminocaproic acid in reference plasma. Using thromboelastographic analysis, VLHL PAI-1 exhibited an IC50 (half maximal inhibitory concentration) of 8.8×10−8 mol/l, while 6-aminocaproic acid showed an IC50 of 1.6×10−4 mol/l. However, at doses of >9.0×10−7 mol/l, VLHL PAI-1 exhibited a delay in the onset of clot formation, which may be attributed to thrombin inhibition by excess PAI-1. The inhibition of tissue plasminogen activator by VLHL PAI-1 demonstrated improved efficacy over 6-aminocaproic acid in mitigating hemorrhage. In addition, patients with a PAI-1 deficiency, which causes blood clots to lyse rapidly resulting in profuse bleeding, may benefit from the application of VLHL PAI-1 as an antihemorrhagic therapy.
Related Links	http://dx.doi.org/10.3892/etm.2015.2399
Ending Page	2343
Page Count	5
Starting Page	2339
File Format	PDF
ISSN	17920981
e-ISSN	17921015
Journal	Experimental and Therapeutic Medicine
Issue Number	6
Volume Number	9
Language	English
Publisher	D.A. Spandidos
Publisher Date	2015-04-01
Access Restriction	Open
Rights Holder	D.A. Spandidos
Subject Keyword	Immunology and Microbiology (miscellaneous) Cancer Research Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research 2400/2401

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