Intense remodeling of extracellular matrix within the varicose vein: the role of gelatinases and vascular endothelial growth factor

Abstract

Background: Increased blood pressure in the varicose veins (VV) can contribute to the overexpression of matrix metalloproteinases (MMPs), affecting the endothelium, smooth muscle, and extracellular matrix of the vein wall. Gelatinases (MMP-2 and MMP-9), hypoxia, and inflammation occurring in the VV wall contribute to the increased expression of vascular endothelial growth factor (VEGF). Aims: Our objective was to analyze the concentration of gelatinases and VEGF in the great saphenous VV wall and plasma of patients. Methods: In total, 65 patients (2nd degree according to clinical state classification, etiology, anatomy, and pathophysiology—CEAP classification) aged 22 to 70 were enrolled. Control veins (n = 10) were collected from the patients who underwent coronary artery bypass graft surgery. Control plasma (n = 20) was obtained from healthy individuals. Gelatinases and VEGF levels were measured with the usage of ELISA method. Results: A significant increase in MMP-9 (11.2 vs. 9.98 ng/mg of protein) and VEGF (41.06 vs. 26 ng/g of protein) concentration in VV wall compared with control veins was observed. A positive correlation between VEGF versus MMP-2 (p = 0.03, r = 0.27) was found in the VV wall. However, no correlation was found between the concentration of VEGF and MMP-9 (p = 0.4, r = 0.11) in the VV wall. In addition, no statistical differences between MMP-9, MMP-2, and VEGF levels in plasma of VV patients compared with controls were noticed. Conclusions: The results of the present study confirm that VV’s patients have altered expression of MMPs and VEGF. Overexpression of MMP-9 and VEGF in the VV wall may contribute to the spreading of inflammatory process and suggests the intense remodeling of extracellular tissue within the VV wall.