Der Einfluss von Matrix-Metalloproteinasen und ihrer Inhibitoren auf die Entstehung chronischer Wunden

The balance between matrix metalloproteinases (MMP´s) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMP´s), play a central role in the process of physiological wound healing. In the present study levels of MMP-2, -8 and -9, as well as TIMP-1 and -2 were measured in fluids of different chronic wounds on day 0, 5, 14, 28, 42 and 56 by ELISA. The analysed wound fluids derive from 45 patients with diabetic foot ulcers, pressure and venous ulcers which were compared to 15 fluids of acute wounds collected form patients on day 2 after split thickness skin grafting. Chronic non healing ulcers were characterized by significantly higher levels of MMP-2, MMP-8 and MMP-9, as well as active MMP-2 and -9, and lower levels of TIMP-1, compared to acute wounds. Generally in patients with chronic wounds persons with good healing ulcers show a significantly lower MMP/TIMP-ratio in contrast to those with impaired wound healing. Thus this ratio might be a predicting factor in the evaluation of wound healing tendencies. This study corroborates the hypothesis that a disturbed balance between MMP´s and TIMP´s with the preponderance of the proteolytic activity of the matrix metalloproteinases causes the development of non healing chronic wounds. The elevated concentrations of MMP-2, MMP-8 and MMP-9 indicate that MMP´s are involved in the pathogenesis of diabetic foot ulcers, decubitus ulcers and leg ulcers caused by chronic venous insufficiency. The low TIMP-1 levels in wound fluids suggest an increased activity of proteinases resulting from a diminished inhibition by their endogenous inhibitors