In contrast to lymphangiogenesis, that is, greatly suppressed in lymphedema and occurs due to the involvement of both VEGF-C and VEGFR-3, fibrosis was modulated in a VEGF-C-independent manner as demonstrated by Avraham et al. (2009) and earlier by Rutkowski et al. (2006), where only weak expression of VEGF-C was detected in the swollen tail of murine models (Avraham et al., 2009). This evidence concerns the gene FLT4 and lymphedema.