Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium
article
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 3.4.21.73; urokinase inhibitor; von Willebrand Factor
Topics
Plasminogen activator inhibitorBlood and hemopoietic systemEndothelium cellHuman cellIn vitro studyPeripheral vascular systemAnimalAntigensBlood ProteinsCulture MediaEndotheliumFactor VIIIGlycoproteinsHumanIsoantigensPlasminogen ActivatorsPlasminogen InactivatorsProtein CSubstrate SpecificityUmbilical ArteriesUmbilical VeinsUrinary Plasminogen Activatorvon Willebrand Factor
TNO Identifier
229795
ISSN
00064971
Source
Blood, 65(2), pp. 444-451.
Pages
444-451
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