Effects of miR‑590 on oxLDL‑induced endothelial cell apoptosis: Roles of p53 and NF‑κB

Mol Med Rep. 2016 Jan;13(1):867-73. doi: 10.3892/mmr.2015.4606. Epub 2015 Nov 23.

Abstract

Oxidized low‑density lipoprotein (oxLDL)‑induced endothelial cell apoptosis is considered to be important in atherogenesis. MicroRNA (miR)‑590 has been reported to inhibit oxLDL‑induced endothelial cell apoptosis. However, the mechanism underlying the inhibition of oxLDL‑induced endothelial cell apoptosis by miR‑590 remains to be elucidated. In the present study, the expression levels of miR‑590 were quantified using reverse transcription‑quantitative polymerase chain reaction analysis. Cell apoptosis was investigated using Hoechst staining and flow cytometry, and cell viability was measured using an MTS method. The protein expression levels of p53, B cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), caspase‑3, lectin‑like low‑density lipoprotein receptor 1 (LOX‑1), p38 mitogen‑activated protein kinase (MAPK) and nuclear factor (NF)‑κB were quantified using western blot analyses. The results of the present study showed that oxLDL treatment inhibited the expression levels of miR‑590 in a time‑dependent and concentration‑dependent manner. The overexpression of miR‑590 inhibited oxLDL‑induced endothelial cell apoptosis, expression of p53 and Bax, reduction of Bcl‑2 and activation of caspase‑3. miR‑590 also inhibited the oxLDL‑induced upregulation of the expression of LOX‑1, overproduction of reactive oxygen species (ROS), phosphoryation of p38MAPK and translocation of NF‑κB. These findings demonstrated the anti‑apoptotic effects of miR‑590 in oxLDL‑treated endothelial cells, with the mechanisms underlying the effects of miR‑590 involved, in part, in the LOX‑1‑ROS‑p38MAPK‑NF‑κB signaling cascade and the p53‑Bcl‑2/Bax‑caspase‑3 signaling pathway. The present study may provide novel insights into the protective properties of miR‑590 in preventing atherosclerosis.

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • I-kappa B Proteins / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Lipoproteins, LDL / pharmacology*
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Proteolysis / drug effects
  • Reactive Oxygen Species / metabolism
  • Transfection
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • bcl-2-Associated X Protein / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • I-kappa B Proteins
  • Lipoproteins, LDL
  • MIRN590 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • oxidized low density lipoprotein
  • L-Lactate Dehydrogenase
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3