VEGFR are receptors for vascular endothelial growth factor (VEGF). The binding of VEGF to VEGFR causes dimerization and autophosphorylation of the receptor.
Aflibercept is a VEGF fusion protein for cardiovascular disease and AMD research.
Aflibercept (VEGF Trap) is a soluble decoy VEGFR constructed by fusing the Ig domains of VEGFR1 and VEGFR2 with the Fc region of human IgG1. Firstly, it inhibits VEGF signaling by reducing VEGF-regulated processes. Secondly, Aflibercept can be used for the research of age-related macular degeneration (AMD) and cardiovascular disease. In some in vitro studies, Aflibercept (500 μg/mL; 24 h and 7 d) shows no toxicity on RPE cells, neither in the MTT assay nor in the trypan blue exclusion assay. Besides, it shows a statistically significant effect on wound healing compared with control in the confluent RPE cell layer with three wounds. In addition, it displays a significantly diminished phagocytosis of opsonized latex beads compared to untreated control. Moreover, Aflibercept (1 and 10 μg/mL; 10 h) inhibits VEGF signaling by reducing VEGF-regulated processes, such as permeability and angiogenesis.
In vivo studies, Aflibercept (18.2 mg/kg and 36.4 mg/kg; i.v. once) affects BP, ROS and eNOS production in mice. Rapidly and dose-dependently elevated BP in mice and markedly impaired endothelial-dependent relaxation (EDR) and resulted in NADPH oxidases 1 (NOX1)- and NADPH oxidases 4 (NOX4)-mediated generation of ROS, decreased the activation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) concurrently with a reduction in nitric oxide (NO) production and elevation of ET-1 levels in mouse aortas. Importantly, Aflibercept (10 mg/kg; 3 h post-middle cerebral artery occlusion (MCAO)) reduces stroke-induced VEGF-A and VEGFR2 expression, and brain edema, and BBB disruption and improves poststroke survival in obese mice.
In conclusion, Aflibercept (VEGF Trap) can inhibit VEGF signaling by inhibiting pathways regulated by VEGF.