VEGFA: a master regulator of angiogenesis

• Gene Information: VEGFA is a protein‑coding gene located on chromosome 6p21.1. It encodes a potent angiogenic growth factor that belongs to the PDGF/VEGF family, with multiple isoforms generated by alternative splicing.
• Protein Expression: VEGFA is secreted by tumour cells, cancer‑associated fibroblasts, tumour‑infiltrating macrophages, and endothelial cells themselves. Its expression is strongly upregulated by hypoxia, oncogenic mutations, and inflammatory mediators such as IL‑6 and TGF‑β, creating a pro‑angiogenic gradient within the tumour microenvironment.
• Signaling Pathway: VEGFA binds with high affinity to receptor tyrosine kinases VEGFR‑1 and VEGFR‑2 on endothelial cells. This drives endothelial cell proliferation, migration, tube formation, vascular permeability, and survival. Additionally, VEGFA promotes the recruitment of immunosuppressive cells and upregulates PD‑L1 on endothelial and tumour cells, directly linking angiogenesis to immune evasion.
• Therapeutic Inhibition: Anti‑VEGFA monoclonal antibodies and small‑molecule multikinase inhibitors targeting VEGFRs block ligand‑receptor binding or downstream kinase activity. 

VEGFA

• The exons 1-8 of mouse Vegfa gene that encode the full-length protein were replaced by human VEGFA exons 1-8 in B-hVEGFA mice(C).

• Mouse VEGFA was detected exclusively in wild-type BALB/cCrSlcNifdc mice.
• Human VEGFA was detected in homozygous B-hVEGFA mice(C), but not in wild-type mice.

Strain specific VEGFA expression analysis in wild-type BALB/cCrSlcNifdc mice and homozygous B-hVEGFA mice(C) by ELISA. Lung homogenates were collected from wild-type BALB/cCrSlcNifdc mice (+/+) (female, n=3, 7-week-old) and homozygous B-hVEGFA mice(C) (H/H) (female, n=3, 7-week-old). Expression level of mouse and human VEGFA were analyzed by ELISA (anti-mouse VEGFA antibody: R&D, MMV00; anti-human VEGFA antibody: R&D, DVE00).