miR-486 is modulated by stretch and increases ventricular growth

JCI Insight. 2019 Sep 12;4(19):e125507. doi: 10.1172/jci.insight.125507.


Perturbations in biomechanical stimuli during cardiac development contribute to congenital cardiac defects such as hypoplastic left heart syndrome (HLHS). This study sought to identify stretch-responsive pathways involved in cardiac development. miRNA-Seq identified miR-486 as being increased in cardiomyocytes exposed to cyclic stretch in vitro. The right ventricles (RVs) of patients with HLHS experienced increased stretch and had a trend toward higher miR-486 levels. Sheep RVs dilated from excessive pulmonary blood flow had 60% more miR-486 compared with control RVs. The left ventricles of newborn mice treated with miR-486 mimic were 16.9%-24.6% larger and displayed a 2.48-fold increase in cardiomyocyte proliferation. miR-486 treatment decreased FoxO1 and Smad signaling while increasing the protein levels of Stat1. Stat1 associated with Gata-4 and serum response factor (Srf), 2 key cardiac transcription factors with protein levels that increase in response to miR-486. This is the first report to our knowledge of a stretch-responsive miRNA that increases the growth of the ventricle in vivo.

Keywords: Cardiology; Cardiovascular disease; Cell Biology; Noncoding RNAs; Proteomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomechanical Phenomena
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Heart Ventricles / growth & development*
  • Heart Ventricles / metabolism
  • Humans
  • Hypoplastic Left Heart Syndrome / genetics*
  • Hypoplastic Left Heart Syndrome / pathology
  • Hypoplastic Left Heart Syndrome / physiopathology
  • Mechanotransduction, Cellular / physiology
  • Mice
  • MicroRNAs / metabolism*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / physiology
  • STAT1 Transcription Factor / metabolism
  • Sheep


  • MIRN486 microRNA, human
  • MIRN486 microRNA, mouse
  • MicroRNAs
  • STAT1 Transcription Factor
  • Stat1 protein, mouse