CXXC5 binds directly to the Flk-1 promoter region and promotes Flk-1 transcriptional activity; correspondingly, CXXC5 is required for BMP signaling-induced Flk-1 expression, motility, and tube formation in endothelial cells; conversely, aberrant expression of CXXC5 results in impaired venous angiogenesis during zebrafish development and the down-regulation of CXXC5 was also observed in vein wall tissue from patients with varicose veins (VV) [4, 84]. This evidence concerns the gene CXXC5 and Varicose veins.