MicroRNA-497 Inhibits Cardiac Hypertrophy by Targeting Sirt4

PLoS One. 2016 Dec 16;11(12):e0168078. doi: 10.1371/journal.pone.0168078. eCollection 2016.

Abstract

Cardiac hypertrophy is an adaptive enlargement of the myocardium in response to overload pressure of heart. From abundant studies, a conclusion is drawn that many microRNAs (miRNAs) are associated with cardiac hypertrophy and heart failure. To investigate the role of microRNA-497 (miR-497) in myocardial hypertrophy, two models were established in this study from cell level to integral level. Cardiac hypertrophy was induced by using angiotensin Ⅱ (Ang Ⅱ) in vitro and was created by transverse abdominal aortic constriction (TAC) in vivo. There was a significant decrease expression of miR-497 in cardiac hypertrophy models. Moreover, overexpression of miR-497 inhibited myocardial hypertrophy both in vitro and in vivo without heart function variation. In addition, luciferase reporter assays demonstrated that Sirt4 was a direct target gene of miR-497. Taking together, our study indicates that miR-497 modulates cardiac hypertrophy by targeting Sirt4 and may serve as a potential therapeutic substance in the course.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cardiomegaly / genetics*
  • Cells, Cultured
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / physiology*
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / metabolism
  • Sirtuins / genetics*
  • Sirtuins / metabolism

Substances

  • MicroRNAs
  • Mitochondrial Proteins
  • mirn497 microRNA, mouse
  • SIRT4 protein, mouse
  • Sirtuins

Grants and funding

The authors received no specific funding for this work.