Knockdown of Sfrp4 attenuates apoptosis to protect against myocardial ischemia/reperfusion injury

J Pharmacol Sci. 2019 May;140(1):14-19. doi: 10.1016/j.jphs.2019.04.003. Epub 2019 Apr 29.

Abstract

Secreted frizzled-related protein (Sfrp) 4 is a protein that involve in cardiac development and several cardiovascular diseases. However, the effect of Sfrp4 in mediating myocardial ischemia/reperfusion injury remains unknown. In this work, adenoviral (Ad)-shSfrp4 adenoviruses was used to knockdown of Sfrp4 in myocardium to examine the role of Sfrp4 in mediating myocardial I/R injury. Knockdown of Sfrp4 in mice attenuated myocardial I/R injury, as indicated by the decrease levels of lactate dehydrogenase and creatine kinase, and increment of ventricular function following I/R injury. Besides, knockdown of Sfrp4 led to a reduction in Bax, active caspase 3, and increase Bcl-2 and c-Myc in cardiac tissue. Knockdown of Sfrp4 lost its protection against I/R injury in mice infected with Ad-dn-AKT. In conclusion, knockdown of Sfrp4 in myocardium attenuated myocardial ischemia and reperfusion injury by AKT signaling pathway.

Keywords: AKT; Apoptosis; Ischemia/reperfusion; Sfrp4.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Gene Knockdown Techniques*
  • Male
  • Mice, Inbred C57BL
  • Myocardial Reperfusion Injury / genetics*
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction / genetics

Substances

  • Proto-Oncogene Proteins
  • Sfrp4 protein, mouse
  • Proto-Oncogene Proteins c-akt