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Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium

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Author: Hinsbergh, V.W.M. van · Bertina, R.M. · Wijngaarden, A. van · Tilburg, N.H. van · Emeis, J.J. · Haverkate, F.
Institution: Gaubius instituut TNO
Source:Blood, 2, 65, 444-451
Identifier: 229795
Keywords: Plasminogen activator inhibitor · Blood and hemopoietic system · Endothelium cell · Human cell · In vitro study · Peripheral vascular system · Animal · Antigens · Blood Proteins · Culture Media · Endothelium · Factor VIII · Glycoproteins · Human · Isoantigens · Plasminogen Activators · Plasminogen Inactivators · Protein C · Substrate Specificity · Umbilical Arteries · Umbilical Veins · Urinary Plasminogen Activator · von Willebrand Factor


Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator-inhibitor. High concentrations of thrombin - but not of factor Xa or IXa - had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor. Chemicals/CAS: plasminogen activator inhibitor, 105844-41-5; plasminogen activator, 9039-53-6; protein C, 60202-16-6; Antigens; Blood Proteins; Culture Media; Factor VIII, 9001-27-8; Glycoproteins; Isoantigens; Plasminogen Activators, EC 3.4.21.-; Plasminogen Inactivators; Protein C; Urinary Plasminogen Activator, EC; urokinase inhibitor; von Willebrand Factor