MicroRNA-19b-1 reverses ischaemia-induced heart failure by inhibiting cardiomyocyte apoptosis and targeting Bcl2 l11/BIM

Heart Vessels. 2019 Jul;34(7):1221-1229. doi: 10.1007/s00380-018-01336-3. Epub 2019 Jan 3.

Abstract

Ischaemia induces cardiac apoptosis and leads to a loss of cardiac function and heart failure after myocardial infarction. MicroRNA-19b-1 (miR-19b-1), a key member of the miR-17/92 cluster, plays crucial roles in inhibiting apoptosis. However, the role of miR-19b-1 in ischaemia-induced heart failure remains unknown. In this study, ischaemia resulted in cardiac apoptosis and the suppression of miR-19b-1 expression, whereas miR-19b-1 overexpression inhibited ischaemia-induced cardiac apoptosis in vivo and in vitro. Moreover, miR-19b-1 not only attenuated the infarct size but also ameliorated heart failure after myocardial infarction, including the changes in the left ventricular ejection fraction and volume load. Mechanically, miR-19-1 targeted and downregulated the mRNA and protein expression of Bcl2l11/BIM, a pro-apoptotic gene of the Bcl-2 family. Together, these results revealed an essential role of miR-19b-1 in ischaemia-induced heart failure.

Keywords: Bcl2-like 11; Cardiac apoptosis; Heart failure; MicroRNA-19b-1; Myocardial infarction.

MeSH terms

  • Animals
  • Apoptosis
  • Bcl-2-Like Protein 11 / genetics*
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation
  • Heart Failure / pathology*
  • Heart Failure / therapy
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / administration & dosage*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myocardial Infarction / etiology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Myocytes, Cardiac / physiology

Substances

  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • MIRN19 microRNA, mouse
  • MicroRNAs