Effect of collagen turnover and matrix metalloproteinase activity on healing of venous leg ulcers

Abstract

The presence of fibrous tissue in poorly healing venous leg ulcers suggests abnormal collagen metabolism. The aim was to determine whether there were differences in collagen turnover and matrix metalloproteinase (MMP) activity between ulcers that healed, those that did not heal and normal skin. Biopsies were taken from the ulcers of 12 patients whose venous ulcers went on to heal and 15 patients whose ulcers failed to heal despite 12 months of compression bandaging. Biopsies were taken from 15 normal controls. Collagen turnover (collagen III N-terminal propeptide (PIIINP) and degraded collagen), and total MMP, MMP-1 and MMP-3 activities were measured. PIIINP and degraded collagen levels were higher in ulcers that healed compared with lesions that failed to heal (P = 0.005 and P < 0.001 respectively) and normal skin (P = 0.003 and P < 0.001). MMP-1 activity was also higher in healing ulcers than resistant ulcers (P < 0.001) and normal skin (P < 0.001). Significantly more total MMP activity was present in all ulcers than in normal skin (P < 0.001), but there was no difference in total MMP (and MMP-3 activity) between ulcers that healed and those that did not. Rapidly healing venous leg ulcers had increased collagen turnover and MMP-1 activity, which appeared to differentiate them from those that failed to heal within 12 months.