Disequilibrium in MMPs and the tissue inhibitor of metalloproteinases in different segments of the varicose great saphenous vein wall.

Abstract

Varicose great saphenous veins (VGSVs) are a common disorder with a high incidence, but the pathogenesis is unclear. This study was designed to measure the changes in matrix metalloproteinases (MMPs) and the tissue inhibitor of metalloproteinases (TIMPs) in different segments from VGSV walls to determine the relationship between MMPs, TIMPs expression, and expansion of the venous wall. Twenty-one VGSV and 12 normal great saphenous vein (GSV) specimens were collected. Venous walls in the two groups, expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 proteins, protein-positive expression ratios, mRNA expression, and protein content were determined by immunohistochemistry, PCR, and western blot. The MMP-2, MMP-9, TIMP-1, and TIMP-2 protein-positive expression ratios, mRNA expression in the upper, middle, and lower segments in the VGSV group were significantly higher than the corresponding regions in the GSV group, respectively. The MMP-2, MMP-9, TIMP-1, and TIMP-2 protein-positive expression ratios, mRNA expression, and protein concentrations in the lower segments in the VGSV group were also significantly higher than the upper and middle segments in the VGSV group and the corresponding regions in the GSV group, respectively. Under high hemodynamics, disequilibrium of MMPs and TIMPs from VGSVs exists within the upper, middle, and lower segments of VGSVs. These results suggested that MMPs and TIMPs participate in the process of venous wall remodeling and may be one of the mechanisms associated with the formation and development in varicose veins.