Corn trypsin inhibitor decreases tissue-type plasminogen activator-mediated fibrinolysis of human plasma.
Corn trypsin inhibitor (CTI) has been considered the molecule of choice to inhibit activated factor XII (FXIIa) during the conduct of experimentation focusing on tissue factor-initiated coagulation. However, CTI-mediated attenuation of fibrinolysis following celite activation of coagulation was observed in pilot studies with the clot lifespan model. The goal of the present study was thus to characterize the mechanism(s) responsible for CTI-mediated hypofibrinolysis. Normal plasma was exposed to 0 or 49.6 microg/ml CTI, with coagulation initiated with celite or tissue factor. Fibrinolysis was initiated with tissue-type plasminogen activator (tPA). Additional experiments utilized plasminogen activator inhibitor 1 deficient or alpha2-antiplasmin-deficient plasma. Coagulation/fibrinolysis kinetics were monitored with the thrombelastography-based clot lifespan model. In addition to delaying the initiation of coagulation, CTI prolonged clot growth time, delayed the onset of lysis, and prolonged clot lysis time in normal plasma after celite activation. Conversely, CTI increased the speed of clot growth, clot strength, and prolonged clot lysis time after tissue factor activation. Experiments with plasma deficient in antifibrinolytic proteins supported a primary inhibition of tPA by CTI. In addition to anti-FXIIa effects following celite activation, CTI likely exerts an anti-tPA effect, which contributed to hypofibrinolysis in this model.
Nielsen
Vance G
VG
Department of Anesthesiology, The University of Alabama at Birmingham, Birmingham, Alabama 35249-6810, USA. vnielsen@uab.edu
D001777:Blood Coagulation / Q000187:drug effects; D007692:Diatomaceous Earth / Q000097:blood / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D010940:Plant Proteins / Q000494:pharmacology*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D010940:Plant Proteins; C052160:trypsin inhibitor, Zea mays; D007692:Diatomaceous Earth; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator