FLT4 and lymphedema: While congenital lymphedema is caused by genetic mutations, acquired lymphedema develops after injury to the lymphatic vasculature.35 A recent study found that acquired lymphedema patients have elevated levels of the proinflammatory mediator leukotriene B4 (LTB4),36 which inhibited VEGFR3 expression and phosphorylation and inhibited NOTCH signaling in LECs.