The role of miR-19b in the inhibition of endothelial cell apoptosis and its relationship with coronary artery disease

Sci Rep. 2015 Oct 13:5:15132. doi: 10.1038/srep15132.

Abstract

The biological effects of microRNAs (miRNAs) and TNF-α in atherosclerosis have been widely studied. The circulating miR-17-92 cluster has been recently shown to be significantly downregulated in patients with injured vascular endothelium. However, it remains unclear whether the miR-17-92 cluster plays a significant role in vascular endothelial repair. The aim of this study was to investigate the relationship between the miR-17-92 cluster and TNF-α-induced endothelial cell apoptosis. We determined that the down-regulation of miR-19b level among patients with coronary artery disease was consistent with miRNA expression changes in endothelial cells following 24 h of TNF-α treatment. In vitro, the overexpression of miR-19b significantly alleviated the endothelial cells apoptosis, whereas the inhibition of miR-19b significantly enhanced apoptosis. The increased levels of Afap1 and caspase7 observed in our apoptosis model could be reduced by miR-19b, and this effect could be due to miR-19b binding 3'-UTRs of Afap1 and caspase7 mRNA. Therefore our results indicate that miR-19b plays a key role in the attenuation of TNF-α-induced endothelial cell apoptosis and that this function is closely linked to the Apaf1/caspase-dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Apoptotic Protease-Activating Factor 1 / chemistry
  • Apoptotic Protease-Activating Factor 1 / genetics
  • Binding Sites
  • Caspase 7 / chemistry
  • Caspase 7 / genetics
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Gene Expression Regulation
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • MicroRNAs / blood
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Multigene Family
  • PTEN Phosphohydrolase / genetics
  • RNA Interference
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Apoptotic Protease-Activating Factor 1
  • MIRN19 microRNA, human
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • PTEN Phosphohydrolase
  • Caspase 7