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Matrix metalloproteinase-9 and urokinase-type plasminogen activator in varicose veins
Ikuko Kosugi1, Hiroshi Urayama, Fuminori Kasashima
1Department of General and Cardiothoracic Surgery, Kanazawa University, School of Medicine, Kanazawa, Japan. ikukok-5@wc4.so-net.ne.jp
Abstract:
The purpose of this study was to evaluate the roles of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) with regard to varicose veins (VVs). Immunohistochemical staining and ELISA were performed on samples from 73 patients with the following leg VVs: 82 greater saphenous veins (GSV) from the groin (GSV groin), 28 GSV from the ankle (GSV ankle), 85 VVs, and 13 normal GSV groin (control [CR]) obtained during coronary artery bypass surgery. Immunohistochemically, MMP-9 was localized in the smooth muscle cells (SMCs) in the tunica media. The ratio of immunopositive cells of MMP-9 in the GSV groin, VVs, and GSV ankle were significantly higher than that of CR. The ratios of immunopositive cells of uPA and uPA receptor (uPAR) were not significantly different among the groups. uPA and uPAR were found to be positive in a different set of SMCs of the MMP-9-positive cells. An ELISA showed that the amount of uPA in the culture of the GSV groin was significantly higher than that in CR. For the remodeling process, MMP-9 may be produced in the VV wall and degrade elastic lamellae and other extracellular components of the venous wall. uPA may be produced by groin tissue of the GSV and flow downward because of valvular incompetence, activating MMP-9 at VV tissues.
Insights
Matrix metalloproteinases-9 (MMP-9) and urokinase-type plasminogen activator (uPA) play roles in varicose veins (VVs). MMP-9 is elevated in VV walls, potentially degrading venous tissue, while uPA may activate MMP-9.
Area of Science:
- Vascular Biology
- Biochemistry
- Pathology
Background:
- Varicose veins (VVs) are a common vascular condition.
- The molecular mechanisms underlying VV development and progression are not fully understood.
- Matrix metalloproteinases (MMPs) and the urokinase-type plasminogen activator (uPA) system are implicated in tissue remodeling.
Purpose of the Study:
- To investigate the expression and localization of MMP-9 and uPA system components in varicose veins.
- To elucidate the potential roles of MMP-9 and uPA in the pathophysiology of VVs.
Main Methods:
- Immunohistochemical staining was performed on venous tissue samples from 73 patients with VVs and 13 controls.
- Enzyme-linked immunosorbent assay (ELISA) was used to quantify uPA levels.
- Samples included greater saphenous veins (GSV) from the groin and ankle, and other VV tissues.
Main Results:
- MMP-9 was significantly upregulated in smooth muscle cells (SMCs) of VV tissues compared to controls.
- uPA and its receptor (uPAR) were expressed in SMCs but showed no significant differences among groups.
- Elevated uPA levels were found in GSV groin cultures compared to controls.
Conclusions:
- MMP-9 is likely produced within the VV wall, contributing to the degradation of extracellular matrix components.
- uPA may be produced in the GSV groin and, due to valvular incompetence, flow into VV tissues, activating MMP-9.
- These findings suggest MMP-9 and uPA are key players in VV pathogenesis and remodeling.