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This study elucidated the mechanism and relation of HIFs and MMPs indicating that increased vein wall tension induces HIFs overexpression and causes an increase in MMPs expression and reduction of venous contraction, leading to progressive venous dilation which may contribute to varicose vein formation (Figure 3) [91]

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SOD3 possess a heparin-binding domain and has high affinity to heparin sulfate proteoglycan, fibulin-5 on the cell surface, collagen, and binds to these molecules directed to the extracellular matrix and endothelial cell surface (Fukai et al., 2002, Nguyen et al., 2004, Petersen et al., 2004)