Fig. 1.

Schematic of VEGF interactions and neutralization. a The compartment model simulates the molecular interactions of two VEGF isoforms (VEGF₁₂₁ and VEGF₁₆₅), receptors (VEGFR1 and VEGFR2), and co-receptors (NRP1 and NRP2). VEGF receptors and co-receptors are expressed on the abluminal and luminal endothelial surfaces, muscle fibers, and tumor cells and are internalized (k _int) and inserted into the cell membrane (s). VEGF₁₂₁ binds to VEGFR1 and VEGFR2 and can form a ternary complex with the coupled VEGFR1–NRP1 complex. VEGF₁₆₅ binds to VEGFR1 and can form the ternary complex VEGF₁₆₅–VEGFR2–NRP by binding to VEGFR2 or one of the NRPs. In addition, VEGF₁₆₅ can be sequestered by GAG chains in the ECM and cellular basement membranes. b VEGF-neutralizing agents bind to the isoforms to block the formation of VEGF/VEGFR complexes and inhibit intracellular angiogenic signaling