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Plasminogen activation in venous leg ulcers.
Br J Dermatol. 2000 Nov; 143(5):930-6.BJ

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.

Authors+Show Affiliations

Department of Dermatology, University of Freiburg, Hauptstr. 7, 79104 Freiburg, Germany. herouy@haut.ukl.uni-freiburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11069499

Citation

Herouy, Y, et al. "Plasminogen Activation in Venous Leg Ulcers." The British Journal of Dermatology, vol. 143, no. 5, 2000, pp. 930-6.
Herouy Y, Trefzer D, Hellstern MO, et al. Plasminogen activation in venous leg ulcers. Br J Dermatol. 2000;143(5):930-6.
Herouy, Y., Trefzer, D., Hellstern, M. O., Stark, G. B., Vanscheidt, W., Schöpf, E., & Norgauer, J. (2000). Plasminogen activation in venous leg ulcers. The British Journal of Dermatology, 143(5), 930-6.
Herouy Y, et al. Plasminogen Activation in Venous Leg Ulcers. Br J Dermatol. 2000;143(5):930-6. PubMed PMID: 11069499.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasminogen activation in venous leg ulcers. AU - Herouy,Y, AU - Trefzer,D, AU - Hellstern,M O, AU - Stark,G B, AU - Vanscheidt,W, AU - Schöpf,E, AU - Norgauer,J, PY - 2000/11/9/pubmed PY - 2001/2/28/medline PY - 2000/11/9/entrez SP - 930 EP - 6 JF - The British journal of dermatology JO - Br J Dermatol VL - 143 IS - 5 N2 - 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. SN - 0007-0963 UR - https://www.unboundmedicine.com/medline/citation/11069499/Plasminogen_activation_in_venous_leg_ulcers_ DB - PRIME DP - Unbound Medicine ER -