Anti-angiogenic effects of ribonucleic acid interference targeting vascular endothelial growth factor and hypoxia-inducible factor-1α

PURPOSE: To compare the in vitro anti,angiogenic effects of inhibiting vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF-1 alpha) using ribonucleic acid (RNA) interference (RNAi). DESIGN: Laboratory investigation. METHODS: VEGF or HIF-1 alpha was antagonized in human retinal pigment epithelial (RPE) cells using RNAi, and then cells were cultured under hypoxia. Angiogenic proteins secreted into the media were measured using enzyme-linked immunosorbent assay. Media from hy poxic RPE cells was used to grow human umbilical vein endothelial cells (HUVECs). Capillary tube formation by HUVECs was quantified and compared to assess the effectiveness of angiogenesis. RESULTS: RNAi targeting VEGF caused a significant decrease in VEGF in addition to several other clinically important angiogenic factors, including angiogenin, interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and tumor growth factor beta(1) (TGF-beta(1)). Although HIF-1 alpha RNAi reduced the production of VEGF, angiogenin, and TGF-beta(1), we observed an increase in the levels of several other angiogenic factors like IL-6, IL-8, and MCP-1. RNAi of VEGF and HIF-1 alpha was effective in inhibiting angiogenesis, al, though the effect was more pronounced for VEGF RNAi. CONCLUSIONS: RNAi of VEGF and HIF-1 alpha may have therapeutic potential in ischemic retinal diseases like diabetic retinopathy. Targeting VEGF seems to have the advantage of decreasing the production of several clinically important angiogenic factors, thereby effectively inhibiting angiogenesis. Antagonism of HIF-1 alpha may lead to the overactivation of alternate transcription factors and their respective gene products, leading to less effective inhibition of angiogenesis.