Serum concentration of matrix metalloproteinases and angiogenic factors in patients with venous leg ulcers

Introduction: Leg ulcers are a frequently observed medical problem affecting 3-5% of the general population over 65 years of age. The most common factor responsible for the development of leg ulcers is chronic venous insufficiency (CVI). It is believed that during the formation of an ulcer there are two processes occurring simultaneously, extracellular matrix (ECM) degradation and angiogenesis in which several proteins including matrix metalloproteinases, angiogenic and regulatory factors are engaged. Aim: To determine the serum concentration of matrix metalloproteinase-1 (MMP-1), -9 (MMP-9), tissue inhibitors of metalloproteinases-1 (TIMP-1), angiogenin and vascular endothelial growth factor (VEGF) in patients suffering from venous leg ulcers and in the healthy control group. Material and methods: The study group consisted of 71 Caucasians (39 patients, 32 controls). To evaluate the serum concentration of MMP-1, MMP-9, TIMP-1, VEGF and angiogenin, the ELISA technique was used. Results: Mean MMP-1 and MMP-9 concentrations in the study group were 14.16 +/- 2.98 and 12.45 +/- 3.85 ng/ml, respectively, and in controls 6.08 +/- 2.51 ng/ml and 6.77 +/- 2.41 ng/ml, respectively and both differences were statistically significant (p < 0.001). There was no significant difference between the study and the control group in TIMP-1 concentration. Mean VEGF and ANG concentrations in the study group were 589.3 +/- 346.2 pg/ml and 1802.0 +/- 415.7 pg/ml, respectively, and in controls 220.3 +/- 110.4 pg/ml and 1229.0 +/- 337.7 pg/ml, respectively and both differences were statistically significant (p < 0.001). Conclusions: Lack of significant differences in the concentration of TIMP-1 between the control and the study group confirms that proteolysis is a hallmark of CVI, but increased concentration of VEGF and angiogenin in the study group compared to the control group shows that angiogenesis occurs simultaneously with ECM remodelling.