The Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in the Wall of Great Saphenous Vein in Patients with Varicose Veins

Abstract

Purpose: Although varicose veins are very common in adults, the mechanism of the disease has not been established. Degradation of the extracellular matrix is regulated by various matrix metallopreteinases (MMPs) and their inhibitors tissue inhibitor of metallaproteinase (TIMPs). This study was performed to analyse the relationship between venous wall degeneration and expression of these matrix proteinases. Methods: Twelve great saphenous vein (GSV) segments from 7 patients without varicose veins (control) and 86 GSV segments from 18 patients (22 limbs) with varicose veins (C 2,4,5 E P A S P R ) were used for this study. Light microscopic examination was used in the evaluation of vein wall degeneration, immunohistochemistry and Western blotting for the expression of MMPs (MMP-1, MMP-2, MMP-9 and MMP-13) and TIMPs (TIMP-1 and TIMP-2), and zymography for gelatinolytic activity of MMP-2 and MMP-9 were performed. Results: MMP-9 was more strongly expressed in the vein wall of both control and patient groups, especially in the endothelial cells and medial muscle layers and TIMP-2 followed. The expression of MMP-9 was closely related to the degree of venous wall degeneration. Activated MMP-2 and MMP-9 were observed in both groups and expressed more in the proximal GSV of the patients. In the Western blotting, the expression of MMP-9 and TIMP-1 were significantly higher than other MMPs and TIMP-2 in the patients with varicose veins. Conclusion: MMP-9 is much more expressed in the wall of degenerative veins. This matrix-degrading enzyme may play an important role in the degeneration of venous wall followed by its remodeling.

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

“…Overexpression of MMP-9 in the VV wall indicates the presence of the inflammatory process. This result supports the previous observations that MMP-9 can contribute to VV development [ 27 ]. The differences between MMP-9 level in study and control plasma were not statistically significant.…”

“…The previous results related to gelatinase activity in VV were ambiguous. The activity of MMP-2 was found to be decreased [ 23 ] or not changed [ 24 – 27 ] in VV wall in comparison with normal tissue. The increased activity of MMP-2 has been also found in the model of VV’s cell line culture [ 28 ].…”

“…Other reports demonstrated no changes [ 26 , 30 ] in activity of MMP-9 or even decreased activity [ 31 ] in the VV. It was postulated that MMP-9 can be involved in the degradation of the vessel wall mainly of the media layer of vascular smooth muscle [ 29 ], whereas Huh et al observed the increased expression of MMP-9 in endothelial cells of vascular smooth muscle [ 27 ]. In our study, a significant increase in MMP-9 concentration within VV wall compared with control no.…”