The Impact of Differential Expression of Extracellular Matrix Metalloproteinase Inducer, Matrix Metalloproteinase-2, Tissue Inhibitor of Matrix Metalloproteinase-2 and PDGF-AA on the Chronicity of Venous Leg Ulcers

Abstract

Non-healing venous ulcers are associated with greater activity MMP-2 activity. The ratio of MMPs to their inhibitors TIMPs, dictate the rate of healing of the ulcers. PDGF-AA activity is associated with ulcer healing, though the mechanism is unclear. EMMPRIN expression in chronic venous ulcers probably parallels the chronicity of the condition rather than propagate it. However, further studies with larger samples are needed.

Non-healing is associated with persistent stimulation of the innate immune response in chronic venous leg ulcers

“…Cytokines demonstrating no distinct differences at the different time-points were sTNFR-I (also known as p55) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) consistent with previous studies [28]. IL-6R levels decreased in non-healing wounds from week 0 to week 4 with an increase again from week 4 to week 8.…”

Inappropriate Angiogenic Response as a Novel Mechanism of Duodenal Ulceration and Impaired Healing

“…It has been implied that the ratio between MMPs and TIMPs is important in wound healing and TIMPs might participate in the tissue-repair process [26]. Two recent studies have demonstrated that high levels of MMP2 and low levels of TIMP-1 and TIMP-2 are associated with non-healing venous leg ulcers [42] and with gastric ulceration induced by ethanol [43]. Taken together, these data and our findings indicate another imbalance of MMP2 and TIMPs in ulceration and impaired healing.…”

Wound Fluid Diagnostics in Diabetic Foot Ulcers

“…Ladwig et al (Ladwig et al 2002) and Liu et al (Liu et al 2009) reported an increased ratio of MMP-9 to TIMP-1 in chronic nonhealing wound fluid compared with healing wounds. Together with the finding that the MMP2:TIMP-2 ratio is elevated in non-healing compared with healing leg ulcers (Mwaura et al 2006), this suggests that a disturbed homeostasis between MMPs and TIMPs might be correlated with the non-healing status. Also, in chronic non-healing diabetic foot ulcers, MMPs and their inhibitors (TIMPs) have received much interest.…”