4.7 Article

MiR-590-5p Inhibits Oxidized-LDL Induced Angiogenesis by Targeting LOX-1

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SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/srep22607

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资金

  1. National Natural Science Foundation of China [81500344]
  2. Anhui Provincial Natural Science Foundation [1508085MH178]
  3. National Natural Science Foundation for Fostering Young Scholars of China [2013KJ25]
  4. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, Washington, DC

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Oxidized low-density lipoprotein (ox-LDL) is, at least in part, responsible for angiogenesis in atherosclerotic regions. This effect of ox-LDL has been shown to be mediated through a specific receptor LOX-1. Here we describe the effect of miR-590-5p on ox-LDL-mediated angiogenesis in in vitro and in vivo settings. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-590-5p mimic or inhibitor followed by treatment with ox-LDL. In other experiments, Marigel plugs were inserted in the mice subcutaneous space. Both in vitro and in vivo studies showed that miR-590-5p mimic (100 nM) inhibited the ox-LDL-mediated angiogenesis (capillary tube formation, cell proliferation and migration as well as pro-angiogenic signals-ROS, MAPKs, pro-inflammatory cytokines and adhesion-related proteins). Of note, miR-590-5p inhibitor (200 nM) had the opposite effects. The inhibitory effect of miR-590-5p on angiogenesis was mediated by inhibition of LOX-1 at translational level. The inhibition of LOX-1 by miR-590-5p was confirmed by luciferase assay. In conclusion, we show that MiR-590-5p inhibits angiogenesis by targeting LOX-1 and suppressing redox-sensitive signals.

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