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

Sci Rep. 2016 Mar 2:6:22607. doi: 10.1038/srep22607.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Movement
  • Cell Proliferation
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lipoproteins, LDL / antagonists & inhibitors*
  • Lipoproteins, LDL / physiology
  • MicroRNAs / physiology*
  • Neovascularization, Pathologic / physiopathology*
  • Scavenger Receptors, Class E / physiology*

Substances

  • Lipoproteins, LDL
  • MIRN590 microRNA, human
  • MicroRNAs
  • OLR1 protein, human
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein