Plasminogen activation in venous leg ulcers

Background Venous leg ulceration results from chronic venous insufficiency of the lower extremities. We recently showed that matrix metalloproteinase (MMP) -2 plays a major part in the pathogenesis of venous leg ulcers. In vi tro activation of recombinant MMP-2 is controlled by the activity of the ur okinase-type plasminogen activator (uPA), which acts as a fibrin-independen t plasminogen activator. The activity of MMP-2 is potentiated by binding of uPA to the uPA receptor (uPAR). Objectives We aimed to clarify the role of plasminogen activation in venous leg ulcers. Methods The expression of uPA, uPAR, the tissue-type plasminogen activator, and plasminogen activator inhibitor (PAI) -1 and PAI-2 was investigated us ing reverse transcription followed by polymerase chain reaction and Western blotting. Results These provided direct evidence of elevated expression of uPA and uP AR at the mRNA and protein levels in venous leg ulcers, in comparison with healthy skin. By immunohistochemistry, elevated expression of uPA and uPAR was detected. Fibrin zymography showed significantly elevated endogenous uP A activity in venous leg ulcers in comparison with healthy controls. Conclusions Our findings indicate venous leg ulcers to be characterized by elevated plasminogen activation, suggesting that this enzyme cascade plays a crucial part in maintaining proteolytic activity in venous leg ulcers.