Imbalanced VEGFR1 and VEGFR2 function in hemangioma

Panel A) In normal endothelial cells (ECs), VEGF binds to VEGFR1 with higher affinity than to VEGFR2. VEGFR1, which is expressed both as soluble and transmembrane forms, acts as a sink for VEGF, thereby decreasing VEGFR2 activity and downstream signals for endothelial cells to proliferate. Panel B) Endothelial cells derived from hemangiomas express aberrant multiprotein complexes - containing integrins and mutated variants of VEGFR2 and TEM8 and possibly also other molecular components (indicated by question mark). These complexes decrease the activity of NFAT, resulting in the downregulation of VEGFR1 expression. As a consequence, more VEGF is available to bind and activate VEGFR2, causing enhanced endothelial cell proliferation.