Role of Endothelial Plasminogen Activators in Fibrinolysis and Repair-Associated Angiogenesis

Two Sides of a Coin
  • Victor W. M. van Hinsbergh
  • Pieter Koolwijk
  • Erik Ponfoort
  • Roeland Hanemaaijer
  • Jef. J. Emeis
  • Teake Kooistra
  • Paul H. A. Quax
Part of the NATO ASI Series book series (NSSA, volume 294)


Fibrin is a temporary matrix, which is formed after wounding a blood vessel and when plasma leaks from blood vessels forming a fibrous exudate, often seen in areas of inflammation and in tumors (Dvorak et al., 1992). The fibrin matrix not only acts as a barrier preventing further blood loss, but also provides a structure in which new microvessels can infiltrate during wound healing. Proper timing of the outgrowth of microvessels as well as the subsequent (partial) disappearance of these vessels is essential to ensure adequate wound healing and to prevent the formation of scar tissue. It is generally believed that plasminogen activators play an important role in the migration and invasion of leukocytes and endothelial cells, and in the dissolution of the fibrin matrix (Kwaan, 1966; Pepper et al., 1990; Koolwijk et al., 1996). Plasminogen activators are serine proteases, which enzymatically convert the zymogen plasminogen into the active protease plasmin, the prime protease that degrades fibrin. The production of plasminogen activators by endothelial cells not only contributes to the proteolytic events related to the formation of microvessels in a wound, but also plays a crucial role in the prevention of thrombosis. If fibrin becomes deposited within the lumen of a blood vessel, cessation of the blood flow may occur accompanied by ischemia and eventually death of the distal tissues. The endothelium contributes considerably to the maintenance of blood fluidity by exposing anticoagulant molecules, by providing factors that interfere with platelet aggregation, and by its ability to stimulate fibrinolysis. Lysis of intravascularly generated fibrin must occur rapidly. However, it should be limited to a local area, because a general elevation of fibrinolysis upon wounding would result in recurrent bleeding.


Endothelial Cell Vascular Endothelial Growth Factor Plasminogen Activator Human Umbilical Vein Endothelial Cell Basic Fibroblast Growth Factor 
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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Victor W. M. van Hinsbergh
    • 1
  • Pieter Koolwijk
    • 1
  • Erik Ponfoort
    • 1
  • Roeland Hanemaaijer
    • 1
  • Jef. J. Emeis
    • 1
  • Teake Kooistra
    • 1
  • Paul H. A. Quax
    • 1
  1. 1.Gaubius Laboratory TNO-PGLeidenThe Netherlands

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