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• W1479798081 abstract "Abstract Protein C inhibitor (PCI) is a heparin-dependent serine protease inhibitor which, in vitro, inhibits activated protein C (APC, urokinase (u-PA) and tissue plasminogen activator (t-PA), plasma kallikrein (KK), thrombin and factors Xa and Ma. We have previously shown in vivo complexes of PCI with APC, u-PA and KK. Here we study the contribution of PCI to the inhibition of t-PA both in vitro and in vivo. PCI complexed to t-PA (t-PA:PCI) was measured by a sandwich ELISA using antibodies directed against each protein in the complex. The formation of t-PA:PCI complexes paralleled the inhibition of t-PA amidolytic activity by PCI in a purified system. In the plasma milieu, after incubation of 8 μg/mL t-PA (final concentration) with human plasma for 2 h at 37°C, in the presence of heparin, the residual t-PA activity was about 38% and plasma contained 0.56 μg/mL t-PA:PCI complexes. To study complex formation in vivo, human plasma samples from patients (n=5) with myocardial infarction were analyzed following infusion of 100 mg recombinant t-PA for 2.5h (10% initial bolus; 40% by a 20min infusion, and 50% by a 2-h infusion). Maximum peak values of t-PA:PCI complexes were measured immediately after the second and third t-PA doses, ranging from 16 to 135 ng/mL. In contrast, during t-PA infusion the level of complexes of t-PA with plasminogen activator inhibitor-1 (t-PA:PAI-1) increased only slightly, from 2.4±1.5 to 7.2±4.6 ng/mL, and reached a maximum mean value of 17.2±20.6 ng/mL 2h post-infusion. PCI antigen decreased during t-PA infusion from 80%±16% to 71%±7%. Protein C antigen levels decreased during t-PA infusion, with the subsequent appearance of complexes between APC and PCI (APC:PCI), and free protein S gradually declined during infusion, reaching levels of 69% of the basal value 2h post-infusion. These data show that in vivo interaction of PCI and t-PA exists, which in turn support the view that PCI may play a role in the regulation of the fibrinolysis pathway. They also show that thrombolytic therapy with t-PA produces activation and a subsequent decrease in protein C antigen levels as well as in free protein S levels." @default.
• W1479798081 created "2016-06-24" @default.
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• W1479798081 date "1993-09-01" @default.
• W1479798081 modified "2023-09-22" @default.
• W1479798081 title "Complex formation between protein c inhibitor and tissue plasminogen activator during thrombolytic therapy" @default.
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• W1479798081 doi "https://doi.org/10.1016/0268-9499(93)90146-m" @default.
• W1479798081 hasPublicationYear "1993" @default.
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