Expression of tissue-type and urokinase-type plasminogen activator activities in chronic venous leg ulcers.

Abstract

Chronic wounds have been shown to exhibit elevated levels of several classes of proteinases. Plasminogen activators (PAs) are proteinases which play a major role in the biological processes involved in wound healing and abnormalities in PAs may play a role in the pathology associated with chronic wounds. Here, we investigated the expression of tPA and uPA activities in chronic venous ulcer biopsies. In 22 patients with chronic venous leg ulcers, punch biopsies were taken from the ulcer base, ulcer margin and uninvolved skin from the thigh of the affected limb and PA activities were assessed using in situ histological zymography. tPA is the main PA activity in uninvolved skin but was reduced in ulcer margin skin and venous leg ulcer tissue compared to normal skin. uPA activity appeared throughout the ulcer margin skin but was at low levels in normal skin. Ulcer base tissue appeared to exhibit a plasminogen-independent proteinase activity not seen in normal or ulcer margin skin. PA activities are altered in and around chronic venous leg ulcers and their distribution suggests that blood vessels in CVI may be damaged and that the tissue is in an inflamed state.