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 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.

Matrix metalloproteinases and venous leg ulceration.

Metalloproteinase-mediated proteolysis plays an important role during the phase of venous ulcer formation and wound repair. Venous ulcers manifest as a breakdown of the collagenous stromal tissue and are highly associated to chronic venous insufficiency. A major change in our understanding of the pathogenesis of venous ulcers occurred with the demonstration of extracellular matrix-degrading activity of matrix metalloproteinases to generate a dermal-epidermal skin defect. These proteases were intensely investigated in preceding stages and during wound repair of venous ulcerations. Different studies have revealed their significance in the process of proteolytic remodeling and recognized their potential importance in finding therapeutic rationales to manage late complications of chronic venous ulcers.

Development and validation of a disease-specific questionnaire on the quality of life of patients with chronic venous insufficiency.

BACKGROUND: Recording of Quality of Life (QoL) is taking on increasing importance in medicine. Although QoL cannot be measured directly, numerous methods studies have demonstrated that important areas of QoL can be addressed by validated questionnaires. The present study was designed to examine a new disease-specific, German-language questionnaire, the Freiburger Questionnaire of QoL in venous diseases (FLQA), with respect to reliability, validity and patient acceptance-among patients with chronic venous insufficiency (CVI). PATIENTS AND METHODS: The FLQA consists of 83 items and differentiates between limitations in QoL in 7 scales: physical complaints, everyday life, social life, emotional status, therapy, satisfaction, occupation. Data were collected from 246 patients with CVI stage I (n = 107), II (n = 75) and III (venous ulcer, n = 64) in the Widmer classification. RESULTS: In the psychometric test, the majority of scales showed little or no top or bottom effect. The internal consistency of the scales was generally high (Cronbach's Alpha in all scales more than alpha = .70 and in 4 scales above alpha = .90). The convergent validity with the Nottingham Health Profile and the ALLTAG was high in several scales. The FLQA showed good discriminant validity and significantly differentiated between the clinical CVI stages in several areas of QoL. The change sensitivity during the course of therapy was also good. In a feasibility test, the acceptance values among patients were high with respect to ease of understanding and description of the QoL areas relevant to them. The mean time to fill out the questionnaire was 21 +/- 6 minutes. CONCLUSION: Overall, the FLQA appears suitable to reliably record characteristics of QoL in patients with CVI in both course and cross-sectional studies.