Pulsed Electromagnetic Fields Combined With Adipose-Derived Stem Cells Protect Ischemic Myocardium by Regulating miR-20a-5p/E2F1/p73 Signaling

Stem Cells. 2023 Jul 14;41(7):724-737. doi: 10.1093/stmcls/sxad037.

Abstract

Myocardial infarction (MI) is a serious threat to human health. Although monotherapy with pulsed electromagnetic fields (PEMFs) or adipose-derived stem cells (ADSCs) has been reported to have positive effect on the treatment of MI, a satisfactory outcome has not yet been achieved. In recent years, combination therapy has attracted widespread interest. Herein, we explored the synergistic therapeutic effect of combination therapy with PEMFs and ADSCs on MI and found that the combination of PEMFs and ADSCs effectively reduced infarct size, inhibited cardiomyocyte apoptosis and protected the cardiac function in mice with MI. In addition, bioinformatics analysis and RT-qPCR showed that the combination therapy could affect apoptosis by regulating the expression of miR-20a-5p. A dual-luciferase reporter gene assay also confirmed that the miR-20a-5p could target E2F transcription factor 1 (E2F1) and inhibit cardiomyocyte apoptosis by regulating the E2F1/p73 signaling pathway. Therefore, our study systematically demonstrated the effectiveness of combination therapy on the inhibition of cardiomyocyte apoptosis by regulating the miR-20a-5p/E2F1/p73 signaling pathway in mice with MI. Thus, our study underscored the effectiveness of the combination of PEMFs and ADSCs and identified miR-20a-5p as a promising therapeutic target for the treatment of MI in the future.

Keywords: E2F transcription factor 1; MiR-20a-5p; adipose-derived mesenchymal stem cells; apoptosis; combination therapy; myocardial infarction; pulsed electromagnetic field.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism
  • Electromagnetic Fields*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Myocardium* / metabolism
  • Signal Transduction

Substances

  • E2F1 Transcription Factor
  • MicroRNAs
  • Mirn20 microRNA, mouse
  • Trp73 protein, mouse