Analysis of matrix metalloproteinase expression in pressure ulcer healing

Amit Kumar Bhagat1, Mukesh Kumar Dwivedi2, Rajeshwar Nath Srivastava2, Abhijit Chandra3 and Saloni Raj4, (1)Department of Surgical Gastroenterology, King George’s Medical University, Lucknow, U.P., India, Lucknow, India, (2)Department of Orthopaedic Surgery, King George’s Medical University, Lucknow, U.P., India, Lucknow, India, (3)Department of Surgical Gastroenterology, King George's Medical University, Lucknow, India, (4)MS Ramiyah Medical College, Bangalore, India, Bangalore, India
Introduction:Matrix metalloproteinases (MMPs) play a major role in wound healing: they can degrade all components of the extracellular matrix. In pressure ulcers there is an excess of MMPs and a decrease of the tissue inhibitors of MMPs (TIMPs). This imbalance is probably one cause of impaired healing. This study was planned to evaluate the levels of MMPs at different follow-up.

Material & Methods: 22 subjects with pressure ulcers were enrolled in the study. Wound tissue was collected regularly during the 9 week follow-up period, for measurement of MMP-8, MMP-9 and TIMP-1. Results were analyzed by the degree of wound healing: good healers (defined by a reduction of 65% wound surface area at 5 weeks) and bad healers (reduction of less than 65% in wound surface area at 5 weeks). Levels of MMPs were analyzed by ELISA.

Results: Levels of MMP-8 and 9 decreased earlier in good healer group. The initial levels of MMP-8 were similar in good and poor healers (P = 0.1) but the level increased significantly at week 2 in good healers (P = 0.03). This was continued in successive weeks. There was a significant correlation between a high ratio of MMP-8/TIMP-1 and good healing (r = 0.65, P= 0.008). Pierson correlation analysis showed that an MMP-8/TIMP-1 ratio of 0.39 best predicted wound healing (sensitivity = 71%, specificity = 87.5%).

Conclusion: A low level of MMP-8 seems essential to wound healing, while an excess of MMP-8 and -9 is deleterious, and could be a target for new topical treatments. The MMP-8/TIMP-1 ratio is a predictor of healing in pressure ulcers.