HIF-α upregulation is the main driver of elevated VEGF in hemangioma endothelial cells and low HIF-α expression is associated with reduced proliferation of hemangioma endothelial cells.[35] Propranolol, the first-line treatment for IH, inhibits endothelial cell proliferation in hemangioma via the HIF-1α-VEGF-A axis.[36] HIF-1α signaling may also mediate autophagy during IH pathogenesis.[37] There is a direct causal relationship between HIF-1α signaling and IH development. This evidence concerns the gene VEGFA and hemangioma.