The physiological and pathological functions of VEGFR3 in cardiac and lymphatic development and related diseases

AbstractVascular endothelial growth factor receptors (VEGFRs) are part of the evolutionarily conserved VEGF signalling pathways that regulate the development and maintenance of the body ’s cardiovascular and lymphovascular systems. VEGFR3, encoded by theFLT4 gene, has an indispensable and well-characterized function in development and establishment of the lymphatic system. Autosomal dominantVEGFR3 mutations, that prevent the receptor functioning as a homodimer, cause one of the major forms of hereditary primary lymphoedema; Milroy disease. Recently, we and others have shown thatFLT4 variants, distinct to those observed in Milroy disease cases, predispose individuals to Tetralogy of Fallot, the most common cyanotic congenital heart disease, demonstrating a novel function for VEGFR3 in early cardiac development. Here, we examine the familiar and emerging roles of VEGFR3 in the development of both lymphovascular and cardiovascular systems, respectively, compare how distinct genetic variants inFLT4 lead to two disparate human conditions, and highlight the research still required to fully understand this multifaceted receptor.

Source: Cardiovascular Research - October 17, 2020 Category: Cardiology Source Type: research