کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5973683 | 1576208 | 2013 | 9 صفحه PDF | دانلود رایگان |
BackgroundCardiomyocyte-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 resultsWild-type (WT) and hSCF/tetracycline transactivator (tTA) transgenic mice (hSCF/tTA) were subjected to myocardial ischemia for 45Â min followed by 3Â h of reperfusion. Infarct size and myocardial apoptosis were decreased in hSCF/tTA compared to WT mice (PÂ <Â 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 (PÂ <Â 0.05), and was associated with higher number of c-kit+ cardiac stem cells (CSCs) (PÂ <Â 0.05). Inhibition of c-kit signaling by ACK2 treatment abolished these protective effects in hSCF/tTA mice.ConclusionsCardiomyocyte-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.
Journal: International Journal of Cardiology - Volume 168, Issue 4, 9 October 2013, Pages 3486-3494