MicroRNA-125a-5p alleviates the deleterious effects of ox-LDL on multiple functions of human brain microvessel endothelial cells

Am J Physiol Cell Physiol. 2017 Feb 1;312(2):C119-C130. doi: 10.1152/ajpcell.00296.2016. Epub 2016 Nov 30.


MicroRNA-125a-5p (miR-125a-5p) could participate in the pathogenesis of vascular diseases. In this study, we investigated the role of miR-125a-5p in oxidized low-density lipoprotein (ox-LDL)-induced functional changes in human brain microvessel endothelial cells (HBMEC). The reactive oxygen species (ROS) production, nitric oxide (NO) generation, senescence, apoptosis, and functions of HBMEC were analyzed. For mechanism study, the epidermal growth factor receptor (EGFR)/extracellular signal-regulated protein kinase (ERK)/p38 mitogen-activated protein kinase (p38 MAPK) pathway and phosphatidylinositol-3-kinase (PI3K)/serine/threonine kinase (Akt)/endothelial nitric oxide synthase (eNOS) pathway were analyzed. Results showed the following: 1) Expression of miR-125a-5p was reduced in ox-LDL-treated HBMEC. 2) Overexpression of miR-125a-5p protected HBMEC from ox-LDL-induced apoptosis, senescence, ROS production, and NO reduction. 3) Overexpression of miR-125a-5p increased HBMEC proliferation, migration, and tube formation, while decreasing HBMEC adhesion to leukocytes, as well as counteracting the effects of ox-LDL on those functions. 4) The levels of EGFR/ERK/p38 MAPK pathway, PI3K/Akt/eNOS pathway, cleaved caspase-3, and adherent molecular ICAM-1 and VCAM-1 were associated with the effects of ox-LDL on these HBMEC functions. In conclusion, miR-125a-5p could counteract the effects of ox-LDL on various HBMEC functions via regulating the EGFR/ERK/p38 MAPK and PI3K/Akt/eNOS pathways and cleaved caspase-3, ICAM-1, and VCAM-1 expression.

Keywords: cell function; human brain microvessel endothelial cells; miR-125a-5p; oxidized low-density lipoprotein; signal pathway.

MeSH terms

  • Apoptosis / physiology
  • Cells, Cultured
  • Cerebral Arteries / cytology
  • Cerebral Arteries / physiology*
  • Endothelial Cells / physiology*
  • Humans
  • Lipoproteins, LDL / metabolism*
  • MAP Kinase Signaling System / physiology
  • MicroRNAs / metabolism*
  • Microvessels / cytology
  • Microvessels / physiology*
  • Neovascularization, Physiologic / physiology
  • Nitric Oxide / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Reactive Oxygen Species / metabolism*


  • Lipoproteins, LDL
  • MIRN125 microRNA, human
  • MicroRNAs
  • Reactive Oxygen Species
  • oxidized low density lipoprotein
  • Nitric Oxide
  • Phosphatidylinositol 3-Kinases