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OBJECTIVES: Imbalance of matrix metalloproteinase enzymes (MMP) and their inhibitors (TIMPs) may contribute to the development of varicose veins. We hypothesised that, histological changes in varicose vein wall correlate with alterations in expression of MMP/TIMP. METHODS: Varicose veins (n=26) were compared with great saphenous vein (GSV) segments (n=11) from arterial bypass, and with arm and neck veins from fistula and carotid operations (n=13). Varicose vein wall thickness was measured, enabling categorisation as atrophic and hypertrophic. MMP-2, MT1-MMP, TIMP-2, and TIMP-3 expression were quantitatively analysed by immunohistochemistry. RESULTS: There was significantly higher expression of TIMP-2 (immunopositive area 4.34% versus 0.26%), linked with connective tissue accumulation in the tunica media of varicose veins as compared with arm and neck vein controls. TIMP-2 and TIMP-3 expression was higher in hypertrophic than atrophic segments (3.2% versus 0.99% for TIMP-2, 1.7% versus 0.08% for TIMP-3). Similarly, TIMP-2 and TIMP-3 had elevated expression in the thicker proximal varicose vein segments compared to distal (4.3% versus 1.3% for TIMP-2 and 0.94% versus 0.41% for TIMP-3). CONCLUSIONS: This study linked morphological changes in varicose vein walls with MMP/TIMP balance. A higher TIMP expression favours deposition of connective tissue and thus thicker vein wall, reducing matrix turnover by suppression of protease activity.

Original publication

DOI

10.1016/j.ejvs.2010.04.028

Type

Journal article

Journal

European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery

Publication Date

12/2010

Volume

40

Pages

754 - 765

Addresses

Department of Surgery and Cancer, Faculty of Medicine, Imperial College, and Department of Histopathology, Charing Cross Hospital, London, UK.

Keywords

Tunica Media, Veins, Connective Tissue, Humans, Varicose Veins, Atrophy, Hypertrophy, Tissue Inhibitor of Metalloproteinase-2, Tissue Inhibitor of Metalloproteinase-3, Immunohistochemistry, Case-Control Studies, Cross-Sectional Studies, Adult, Aged, Aged, 80 and over, Middle Aged, London, Female, Male, Matrix Metalloproteinase 2, Matrix Metalloproteinase 14, Young Adult