Cardiomyocyte-specific overexpression of human stem cell factor protects against myocardial ischemia and reperfusion injury

Int J Cardiol. 2013 Oct 9;168(4):3486-94. doi: 10.1016/j.ijcard.2013.04.165. Epub 2013 May 13.


Background: Cardiomyocyte-specific overexpression of human membrane-associated stem cell factor (hSCF) improves cardiac function post-myocardial infarction. However, whether hSCF overexpression protects the heart from ischemia and reperfusion (I/R) injury is unknown. We aimed to investigate the effects of cardiomyocyte-specific overexpression of hSCF on cardiac injury after acute myocardial I/R and related cellular and molecular signaling mechanisms.

Methods and results: Wild-type (WT) and hSCF/tetracycline transactivator (tTA) transgenic mice (hSCF/tTA) were subjected to myocardial ischemia for 45 min followed by 3 h of reperfusion. Infarct size and myocardial apoptosis were decreased in hSCF/tTA compared to WT mice (P<0.05). Furthermore, these cardioprotective effects in the hSCF/tTA mice were abrogated by doxycycline, which turned off hSCF overexpression, and by a PI3 kinase inhibitor LY294002. Myocardial expression of insulin-like growth factor (IGF)-1 and hepatocyte growth factor (HGF), which are upstream activators of Akt signaling, was significantly increased in hSCF/tTA compared to WT mice after I/R (P<0.05), and was associated with higher number of c-kit(+) cardiac stem cells (CSCs) (P<0.05). Inhibition of c-kit signaling by ACK2 treatment abolished these protective effects in hSCF/tTA mice.

Conclusions: Cardiomyocyte-specific overexpression of hSCF protects the heart from I/R injury. The cardioprotective effects of hSCF overexpression are mediated by increased c-kit(+) CSCs, enhanced growth factor expression and activation of Akt signaling pathway.

Keywords: Akt; Ischemia/reperfusion injury; Stem cell factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotonic Agents / metabolism
  • Gene Expression Regulation*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Myocardial Ischemia / genetics
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / prevention & control
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Stem Cell Factor / biosynthesis*
  • Stem Cell Factor / genetics*


  • Cardiotonic Agents
  • Stem Cell Factor