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Xuri Li; Inhibition of VEGF-A upregulates other VEGF family members and VEGF receptors. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2630.
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Anti vascular endothelial growth factor A（Anti-VEGF-A） therapy has been used in the clinic to treat patients with neovascular diseases. However, it is thus far unclear whether inhibition of vascular endothelial growth factor A（VEGF-A） affects the expression of the other vascular endothelial growth factor（VEGF） family members and their receptors. To this end, we used both cultured cells in vitro and mouse eyes in vivo and investigated into this.
Cultured vascular endothelial cells and macrophages and a laser-induced choroidal neovascularization (CNV) model was used in this study.
We found that in cultured vascular endothelial cells and macrophages, inhibition of VEGF-A by a neutralizing antibody (nab) increased the expression levels of VEGF-B, PlGF, and their receptors VEGFR1 and Np1. Indeed, this finding is confirmed in vivo. Using a mouse CNV model, we also found that inhibition of VEGF-A by VEGF-A nab increased PlGF expression. Together, our findings suggest that inhibition of VEGF-A alone may not be sufficient to inhibit angiogenesis. We subsequently used a laser-induced CNV mouse model and tested an anti-angiogenic drug Conbercept that can block VEGF-A, VEGF-B, PlGF and VEGF-C simultaneously. We found that at the same dose, Conbercept resulted in a better inhibition of CNV as compared with VEGF-A nab.
Our data show that inhibition of VEGF-A can lead to compensatory upregulation of other VEGF family members, and simultaneous inhibition of multiple VEGF family members gave a better inhibition of CNV.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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