PECULIARITIES OF CHANGES IN THE BALANCE OF THE ANGIOGENESIS REGULATORS AND ACTIVITIES OF MATRIX METALOPROTEINASES -2, -9 IN CHRONIC ULCERS IN DIABETIC PATIENTS

Abstract

Abstract. Aim. Chronic diabetic foot ulcers are serious complications of diabetes mellitus, which account for 85 % of purulent-necrotic lesions of the lower extremities. This study was conducted to assess the levels of protein regulators of angiogenesis (vascular endothelial growth factor, or VEGF, hypoxia-inducible factor-1α and angiostatins) and to assess the activity of matrix metalloproteinases (MMPs) (gelatinases MMP-2 and -9) in chronic wound tissue of diabetic patients. Methods and materials: VEGF and angiostatin levels were analyzed by western blot, MMP activities were assessed by gelatin zymography. We found that the tissue of diabetic wounds is characterized by a reduced level of VEGF (by 2.5 times compared to acute wound tissue P<0.01) and increased levels of angiostatin, which are not detected in non-diabetic wounds. In the tissues of diabetic wounds, there is an approximately 5-fold increase in the activity of MMP-2 and -9 compared to intact skin tissue. The expression of the central regulator of hypoxia-related processes HIF-1α was increased by 4.4 times in diabetic wounds compared to the this value in acute wounds (P<0.01). Conclusions. We established an inverse correlation between the levels of HIF-1α and VEGF in dermal biopsies collected from chronic skin lesions. The obtained results indicate that increased production of angiogenic inhibitor, angiostatin, can counteract VEGF-induced proangiogenic signaling and, together with MMP hyperactivation, may contribute to poor ischemic ulcer healing.