Local inhibition of microRNA-24 improves reparative angiogenesis and left ventricle remodeling and function in mice with myocardial infarction

Mol Ther. 2013 Jul;21(7):1390-402. doi: 10.1038/mt.2013.89. Epub 2013 Jun 18.


Myocardial infarction (MI) is the leading cause of death worldwide. MicroRNAs regulate the expression of their target genes, thus mediating a plethora of pathophysiological functions. Recently, miRNA-24 emerged as an important but controversial miRNA involved in post-MI responses. Here, we aimed at clarifying the effect of adenovirus-mediate intra-myocardial delivery of a decoy for miRNA-24 in a mouse MI model and to investigate the impact of miRNA-24 inhibition on angiogenesis and cardiovascular apoptosis. After MI induction, miRNA-24 expression was lower in the peri-infarct tissue and its resident cardiomyocytes and fibroblasts; while it increased in endothelial cells (ECs). Local adenovirus-mediated miRNA-24 decoy delivery increased angiogenesis and blood perfusion in the peri-infarct myocardium, reduced infarct size, induced fibroblast apopotosis and overall improved cardiac function. Notwithstanding these beneficial effects, miRNA-24 decoy increased cardiomyocytes apoptosis. In vitro, miRNA-24 inhibition enhanced ECs survival, proliferation and networking in capillary-like tubes and induced cardiomyocyte and fibroblast apoptosis. Finally, we identified eNOS as a novel direct target of miR-24 in human cultured ECs and in vivo. Our findings suggest that miRNA-24 inhibition exerts distinct biological effects on ECs, cardiomyocytes and fibroblasts. The overall result of post-infarction local miRNA-24 inhibition appears to be therapeutic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Mice
  • MicroRNAs / antagonists & inhibitors*
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / genetics*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Neovascularization, Physiologic / drug effects*
  • Nitric Oxide Synthase Type III / metabolism
  • Ventricular Remodeling / drug effects*


  • MicroRNAs
  • Mirn24 microRNA, mouse
  • Nitric Oxide Synthase Type III