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Mechanism of protein C-dependent clot lysis: role of plasminogen activator inhibitor

Academic Article
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Overview

authors

  • Sakata, Y.
  • Loskutoff, David J.
  • Gladson, C. L.
  • Hekman, C. M.
  • Griffin, John

publication date

  • 1986

journal

  • Blood  Journal

abstract

  • The mechanism by which activated protein C stimulates fibrinolysis was studied in a simple radiolabeled clot lysis assay system containing purified tissue-type plasminogen activator, bovine endothelial plasminogen activator inhibitor (PAI), plasminogen, 125I-fibrinogen and thrombin. Fibrinolysis was greatly enhanced by the addition of purified bovine activated protein C; however, in the absence of PAI, activated protein C did not stimulate clot lysis, thus implicating this inhibitor in the mechanism. In clot lysis assay systems containing washed human platelets as a source of PAI, bovine-activated protein C-dependent fibrinolysis was associated with a marked decrease in PAI activity as detected using reverse fibrin autography. Bovine-activated protein C also decreased PAI activity of whole blood and of serum. In contrast to the bovine molecule, human-activated protein C was much less profibrinolytic in these clot lysis assay systems and much less potent in causing the neutralization of PAI. This species specificity of activated protein C in clot lysis assays reflect the known in vivo profibrinolytic species specificity. When purified bovine-activated protein C was mixed with purified PAI, complex formation was demonstrated using immunoblotting techniques after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. These observations suggest that a major mechanism for bovine protein C-dependent fibrinolysis in in vitro clot lysis assays involves a direct neutralization of PAI by activated protein C.

subject areas

  • Blood Platelets
  • Fibrinogen
  • Fibrinolysis
  • Glycoproteins
  • Humans
  • In Vitro Techniques
  • Plasminogen
  • Plasminogen Activators
  • Plasminogen Inactivators
  • Protein C
  • Thrombin
  • Tissue Plasminogen Activator
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Identity

International Standard Serial Number (ISSN)

  • 0006-4971

PubMed ID

  • 3096399
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Additional Document Info

start page

  • 1218

end page

  • 1223

volume

  • 68

issue

  • 6

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