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

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

Author information

1
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.

Abstract

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

PMID:
23680593
DOI:
10.1016/j.ijcard.2013.04.165
[Indexed for MEDLINE]

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