Author/Authors :
Farzin Forooghian، نويسنده , , Bikul Da، نويسنده ,
Abstract :
Purpoe
To compare the in vitro anti-angiogenic effect of inhibiting vacular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) uing ribonucleic acid (RNA) interference (RNAi).
Deign
Laboratory invetigation.
Method
VEGF or HIF-1α wa antagonized in human retinal pigment epithelial (RPE) cell uing RNAi, and then cell were cultured under hypoxia. Angiogenic protein ecreted into the media were meaured uing enzyme-linked immunoorbent aay. Media from hypoxic RPE cell wa ued to grow human umbilical vein endothelial cell (HUVEC). Capillary tube formation by HUVEC wa quantified and compared to ae the effectivene of angiogenei.
Reult
RNAi targeting VEGF caued a ignificant decreae in VEGF in addition to everal other clinically important angiogenic factor, including angiogenin, interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and tumor growth factor β1 (TGF-β1). Although HIF-1α RNAi reduced the production of VEGF, angiogenin, and TGF-β1, we oberved an increae in the level of everal other angiogenic factor like IL-6, IL-8, and MCP-1. RNAi of VEGF and HIF-1α wa effective in inhibiting angiogenei, although the effect wa more pronounced for VEGF RNAi.
Concluion
RNAi of VEGF and HIF-1α may have therapeutic potential in ichemic retinal dieae like diabetic retinopathy. Targeting VEGF eem to have the advantage of decreaing the production of everal clinically important angiogenic factor, thereby effectively inhibiting angiogenei. Antagonim of HIF-1α may lead to the overactivation of alternate trancription factor and their repective gene product, leading to le effective inhibition of angiogenei.