title: The FVII activating protease cleaves single-chain plasminogen activators.
abstract: A serine protease isolated from plasma sharing structural characteristics with a hepatocyte growth factor activator-like protease has been demonstrated recently to activate FVII. Accordingly, it was named 'FVII activator'. Until now an impact of this protease on the fibrinolytic system has not been reported. We islolated the protease from cryo-poor plasma by subsequent ion exchange chromatography and adsorption to immobilized heparin and/or aprotinin. Incubation of single-chain plasminogen activators (sc-PAs) with the FVII activator revealed significant activation of urokinase sc-PA (scu-PA) and tissue sc-PA (sct-PA) in vitro. It was enhanced in the presence of calcium and heparin. Compared to kallikrein, a more efficient activation of scu-PA was observed, whereas sct-PA appeared to be a poorer substrate for the FVI activator. At low protease concentrations and in the presence of heparin the scu-PA activation was comparable to plasmin. Employing recalcified whole blood thrombelastography, the lysis of initially formed fibrin was observed after addition of a combination of scu-PA and the FVII activator, whereas the scu-PA alone had a negligible effect at the concentration used. The study results as presented demonstrate that the FVII activator is a potent activator of sc-PAs in vitro. Whether it plays a physiological role in fibrinolysis deserves further investigation. Its comparatively high affinity to heparin assumes a function in cell surface or matrix events.
authors.affiliation: Aventis Behring GmbH, Research, Marburg, Germany. juergen.roemisch@aventis.com
authors.forename: J
authors.initials: J
authors.lastname: Römisch
authors.forename: S
authors.initials: S
authors.lastname: Vermöhlen
authors.forename: A
authors.initials: A
authors.lastname: Feussner
authors.forename: H
authors.initials: H
authors.lastname: Stöhr
mesh_terms: D001779:Blood Coagulation Factors / Q000378:metabolism; D001780:Blood Coagulation Tests; D002863:Chromogenic Compounds / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005167:Factor VII / Q000187:drug effects / Q000378:metabolism*; D015942:Factor VIIa / Q000187:drug effects / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism; D012697:Serine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D001779:Blood Coagulation Factors; D002863:Chromogenic Compounds; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; C041319:isoleucyl-prolyl-arginine-4-nitroanilide; D005167:Factor VII; D012697:Serine Endopeptidases; D015942:Factor VIIa; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator