Vascular endothelial growth factor A signaling axis (VEGFA)

The Vascular endothelial growth factor A (VEGFA) signaling axis is a fundamental regulator of angiogenesis, vasculogenesis, and vascular permeability [3, 8]. It primarily functions through the binding of the VEGFA ligand to its high-affinity receptor tyrosine kinases, VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1), with VEGFR2 serving as the predominant mediator of angiogenic signaling [5, 13]. In healthy tissues, this axis is critical for processes such as embryonic development, wound healing, and the menstrual cycle [8, 16]. Pathologically, the axis is hijacked by tumors to promote neovascularization, facilitating tumor growth and metastasis, and is also implicated in ocular diseases like wet age-related macular degeneration (AMD) and diabetic retinopathy [3, 14]. Therapeutic interventions targeting this axis include monoclonal antibodies (e.g., bevacizumab), decoy receptors (e.g., aflibercept), and small-molecule tyrosine kinase inhibitors (e.g., sunitinib, sorafenib) [4, 10]. While these treatments have revolutionized oncology and ophthalmology, they are associated with distinct safety concerns, including hypertension, proteinuria, and impaired wound healing, due to the essential role of VEGFA in maintaining vascular homeostasis [10, 17].

Other names

VEGFVascular permeability factor (VPF)FolliculostatinVEGF-AMVCD1

Neutralization of VEGFA ligand to prevent receptor binding; Inhibition of VEGFR tyrosine kinase activity; Competitive inhibition of VEGFR2 binding