MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity

Biochem Biophys Res Commun. 2010 Mar 19;393(4):643-8. doi: 10.1016/j.bbrc.2010.02.045. Epub 2010 Feb 12.

Abstract

Mechanical forces associated with blood flow play an important role in regulating vascular signaling and gene expression in endothelial cells (ECs). MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. miRNAs are known to have an important role in modulating EC biology, but their expression and functions in cells subjected to shear stress conditions are unknown. We sought to determine the miRNA expression profile in human ECs subjected to unidirectional shear stress and define the role of miR-21 in shear stress-induced changes in EC function. TLDA array and qRT-PCR analysis performed on HUVECs exposed to prolonged unidirectional shear stress (USS, 24h, 15 dynes/cm(2)) identified 13 miRNAs whose expression was significantly upregulated (p<0.05). The miRNA with the greatest change was miR-21; it was increased 5.2-fold (p=0.002) in USS-treated versus control cells. Western analysis demonstrated that PTEN, a known target of miR-21, was downregulated in HUVECs exposed to USS or transfected with pre-miR-21. Importantly, HUVECs overexpressing miR-21 had decreased apoptosis and increased eNOS phosphorylation and nitric oxide (NO(*)) production. These data demonstrate that shear stress forces regulate the expression of miRNAs in ECs, and that miR-21 influences endothelial biology by decreasing apoptosis and activating the NO(*) pathway. These studies advance our understanding of the mechanisms by which shear stress forces modulate vascular homeostasis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Apoptosis*
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiology*
  • Gene Expression Regulation, Enzymologic
  • Homeostasis
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type III / genetics*
  • Nitric Oxide Synthase Type III / metabolism
  • Oligonucleotide Array Sequence Analysis
  • PTEN Phosphohydrolase / biosynthesis
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Shear Strength*

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • Nitric Oxide
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • PTEN Phosphohydrolase
  • PTEN protein, human