Overexpression of cathepsin K and vascular endothelial growth factor in chronic venous ulcerations

Abstract

Introduction: Chronic venous disease (CVD) is a disabling condition affecting about 1% to 3% of the general population. Besides varicose veins, CVD can result also in the formation of severe skin lesions, especially venous ulcerations (VU). The exact mechanism of VU is still unknown. Aim: To evaluate immunoexpression of vascular endothelial growth factor (VEGF) and cathepsin K in healthy individuals and patients with VU. Material and methods: The study included 12 patients with venous ulcers and 10 healthy individuals who served as controls; both groups were sex-and age-matched. Biopsy samples were obtained from lower leg areas and submitted to histochemical analysis. Results: There was a significant difference between the study group and the control group in cathepsin K expression (1.007 ±0.3 vs. 0.22 ±0.2, respectively, p < 0.001) and VEGF expression (1.17 ±0.59 vs. 0.27 ±0.19, respectively, p < 0.001). Additionally, the microvessel density (per mm 2 ) differed significantly between the study group and the control group (97.6 ±28.81 vs. 59.32 ±12.71, respectively, p < 0.001). We found no correlation between cathepsin K and microvessel density, and cathepsin K and VEGF in both groups, but there was a significant correlation between microvessel density and VEGF immunoexpression in the study group (r = 0.82, p = 0.002). Conclusions: Increased immunoexpression of VEGF and cathepsin K suggests that both of these proteins may play a role in VU development.

A simplified method for monitoring cytokines in wound fluid

“…The cells responsible for the secretion of cytokines have been only sparsely described in the literature on leg ulcers 27–30 . In acute wounds, keratinocytes are prominent cytokine producers at the wound edge 31,32 and of macrophages and fibroblasts in the wound bed 33,34 .…”

“…Admittedly, the Zillmer method 5 might not provide a realistic snapshot of cytokine concentrations in wounds. The cytokine levels in WF reflect the net results of several concurrent processes in which secretion and degradation are important 29 . VEGF secretion might have declined over the 23‐h collection period.…”

“…The cells responsible for the secretion of cytokines have been only sparsely described in the literature on leg ulcers. 27 , 28 , 29 , 30 In acute wounds, keratinocytes are prominent cytokine producers at the wound edge 31 , 32 and of macrophages and fibroblasts in the wound bed. 33 , 34 The senescent fibroblast phenotype commonly found in nonhealing leg ulcers contributes to the proinflammatory environment.…”

“…The cytokine levels in WF reflect the net results of several concurrent processes in which secretion and degradation are important. 29 VEGF secretion might have declined over the 23‐h collection period.…”