Andrographolide attenuates choroidal neovascularization by inhibiting the HIF-1α/VEGF signaling pathway.

Choroidal neovascularization (CNV), a characteristic of wet age-related macular degeneration (AMD), leads to severe vision loss amongst the elderly in the developed countries. Currently, the premier treatment for AMD is anti-VEGF therapy, which has limited efficacy, and is still controversial. Previous studies have showed that Andrographolide (Andro) had various biological effects, including anti-angiogenesis, anti-inflammation, and antioxidant. However, the effect of Andro on the formation of CNV has not been studied thus far. Here our results showed that Andro reduced the expression levels of HIF-1α and VEGF in the RF/6A cells chemical hypoxia model and the laser-induced CNV mouse model. Moreover, Andro inhibited the tube formation activity of RF/6A cells under hypoxic conditions. Furthermore, intraperitoneal injection of Andro reduced the severity of choroidal vascular leakage and the size of CNV in the laser-induced CNV mouse model, indicating that Andro attenuated the development of CNV by inhibiting the HIF-1α/VEGF signaling pathway. These results suggest that Andro could be a potential novel therapeutic agent for AMD.

Cui K ，Liu J ，Huang L ，Qin B ，Yang X ，Li L ，Liu Y ，Gu J ，Wu W ，Yu Y ，Sang A ... -  《-》

Inhibition of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor by Chrysin in a Rat Model of Choroidal Neovascularization.

Song JH ，Moon KY ，Lee SC ，Kim SS ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Inhibition of RACK1 ameliorates choroidal neovascularization formation in vitro and in vivo.

Liu X ，Zhu M ，Yang X ，Wang Y ，Qin B ，Cui C ，Chen H ，Sang A ... -  《-》

CBX7 promotes choroidal neovascularization by activating the HIF-1α/VEGF pathway in choroidal vascular endothelial cells.

Vascular endothelial growth factor (VEGF) signaling is crucial for choroidal neovascularization (CNV), a major pathological feature of neovascular age-related macular degeneration (nAMD). Gene transcription of VEGF is mainly regulated by hypoxia-inducible factor 1-alpha (HIF-1α). The chromobox (CBX) family polycomb protein (Pc) subgroup includes CBX2, CBX4, CBX6, CBX7, and CBX8. CBX4 enhances hypoxia-induced VEGF expression and angiogenesis in hepatocellular carcinoma (HCC) cells by increasing HIF-1α's transcriptional activity. The objective of the study was to examine the functions of members of the CBX family Pc subgroup in choroidal vascular endothelial cells (CVECs) during CNV. CBX4 and CBX7 expression was up-regulated in hypoxic human choroidal vascular endothelial cells (HCVECs). In HCVECs, CBX7 facilitated HIF-1α transcription and expression, while CBX4 did not. In HCVECs, CBX7 stimulated HIF-1α's nuclear translocation and transcriptional activity, which in turn stimulated VEGF transcription and expression. The CBX7/HIF-1α/VEGF pathway promoted the migration, proliferation, and tube formation of HCVECs. The CBX7/HIF-1α/VEGF pathway was up-regulated in CVECs and in the mouse model with laser-induced CNV. Mouse CNV was lessened by the blockade of CBX7 through the down-regulation of HIF-1α/VEGF. In conclusion, CBX7 enhanced pro-angiogenic behaviors of hypoxic CVECs by up-regulating the HIF-1α/VEGF pathway, which contributing to the formation of mouse laser-induced CNV.

Wang Q ，Zhu M ，Li W ，Guo Y ，Lou H ，Zhang J ，Xu Y ，Zeng B ，Wen X ，Ji X ，Xie L ... -  《-》

Influence of Dll4 via HIF-1α-VEGF signaling on the angiogenesis of choroidal neovascularization under hypoxic conditions.

Dong X ，Wang YS ，Dou GR ，Hou HY ，Shi YY ，Zhang R ，Ma K ，Wu L ，Yao LB ，Cai Y ，Zhang J ... -  《-》