Tissue and urokinase plasminogen activators in the environs of venous and ischaemic leg ulcers

Abstract

Urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA) were assayed in biopsies from the base, edge and adjacent skin of ischaemic and venous ulcers using a functional bioimmunoassay and a standard immunoassay. Two series of 14 biopsies were examined: from seven venous and seven ischaemic ulcers in the first series, eight venous and six ischaemic in the second. It was found that tPA was detected in only four samples of ulcer edge using the bioimmunoassay and in no sample by the standard immunoassay. By contrast, uPA was detected in all but one ulcer edge biopsy and at a significantly lower median concentration in the adjacent skin (16.9 units/g) than the ulcer edge (26.1 units/g) or base (32.3 units/g) (both P < 0.01). Levels of uPA were greater in the edge and base of venous compared with ischaemic ulcers. The predominant plasminogen activator in chronic leg ulcers is uPA; this activator may play an important role in wound healing.

Epithelial tissue-type plasminogen activator expression, unlike that of urokinase, its receptor, and plasminogen activator inhibitor-1, is increased in chronic venous ulcers

“…To our knowledge, this is the first report linking tPA expression to human wound healing in vivo . In previous studies tPA expression was not detected in healing human wounds, 3,8 and enzymatic studies have proposed uPA as the predominant PA present in wounds and ulcers 18,28–30 . In our study, tPA antigen and mRNA colocalization and, in addition, negative staining with a sense tPA probe and different localization of other probes and antibodies, indicated specific tPA staining.…”

Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-Isoquinolinylguanidines

“…1 An inhibitor of uPA may have a therapeutic role in disease situations where uPA-driven degradation of extracellular matrix, or uPA-dependent cell migration is thought to be important--including tumour growth, metastasis, angiogenesis and chronic wounds. [2][3][4][5][6][7] The closely related enzyme tPA also acts via activation of plasminogen to plasmin and is a key component of the fibrinolytic cascade. 8;9 Achievement of adequate selectivity over both tPA and plasmin is therefore an important requirement in a therapeutically valuable uPA inhibitor.…”

Plasminogen activation in venous leg ulcers

“…Despite considerable evidence localizing uPA in venous leg ulcers, 14 and in vitro data suggesting plasminogen activation to be important for MMP‐2 activation, there have been no studies of tissue‐related plasminogen activation in venous leg ulcers. We therefore analysed the expression and functional state of fibrinolytic factors in tissue specimens from patients with venous leg ulcers.…”