Plasminogen activation in venous leg ulcers

Authors: Herouy Y.; Trefzer D.; Hellstern M.O.; Stark G.B.; Vanscheidt W.; Schöpf E.; Norgauer J.

Source: British Journal of Dermatology, Volume 143, Number 5, November 2000 , pp. 930-936(7)

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Abstract:

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 vitro activation of recombinant MMP-2 is controlled by the activity of the urokinase-type plasminogen activator (uPA), which acts as a fibrin-independent 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 using reverse transcription followed by polymerase chain reaction and Western blotting.

Results These provided direct evidence of elevated expression of uPA and uPAR 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 uPA 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.

Keywords: fibrinolytic factors; matrix metalloproteinases; venous ulceration

Language: English

Document Type: Research article

Publication date: 2000-11-01