Anti-angiogenic effect of rapamycin in mouse oxygen-induced retinopathy is mediated through suppression of HIF-1alpha/VEGF pathway

作者：Sun, Yi Zhou; Liu, Lei; Cai, Na; Liu, Ning Ning^*

来源：International Journal of Clinical and Experimental Pathology, 2017, 10(10): 10167-10175.

• Rapamycin
• human umbilical vein endothelial cells
• hypoxia-inducible factor-1alpha
• vascular endothelial growth factor
• retinal neovascularization

Hypoxia-inducible factor-1alpha (HIF-1 alpha)-vascular endothelial growth factor (VEGF) pathway, a downstream of mammalian target of rapamycin (mTOR), plays a major role in the formation of pathological retinal angiogenesis. Rapamycin (RAPA), a highly specific inhibitor of mTOR, is widely used in cancer studies for its antiangiogenic activity. However, the inhibitory effects of RAPA on the HIF-1 alpha-VEGF pathway in retinal tissues were rarely researched. The study aimed to investigate the efficacy and potential mechanisms of RAPA in inhibiting retinal neovascularization. Human umbilical vein endothelial cells (HUVECs) were treated with hypoxia and in the presence of different concentrations of RAPA. RAPA was injected intraperitoneally in oxygen-induced retinopathy (OIR) C57BL/6 mice from postnatal day 12 (P12) to P17. The proliferation of HUVECs, the protein and mRNA expressions of HIF-1 alpha and VEGF were evaluated in HUVECs or OIR mice using MTT assay, ELISA, immunohistochemistry, Western-blot and real-time PCR. Histological methods were used to count blood vessel profiles in the inner retina. RAPA inhibited HUVECs proliferation and retinal neovascularization by reducing protein and mRNA expressions of HIF-1 alpha and VEGF. RAPA suppresses hypoxia-induced HUVECs cell proliferation and pathological ocular angiogenesis through a mechanism linked to the targeting of HIF-1 alpha/VEGF signaling.

• 出版日期2017
• 单位中国医科大学