Genes associated with lymphangiogenesis and the junctional paracellular permeability of vessels such as GJA1 [28,29,30,31,32], CLDN5 [33,34] and VEGFR3 [35,36,37] were found upregulated only in secondary lymphedema, where true edema is present. This evidence concerns the gene CLDN5 and lymphedema.