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Circ Heart Fail. 2014 Sep;7(5):831-42. doi: 10.1161/CIRCHEARTFAILURE.114.001423. Epub 2014 Aug 8.

Cardiac-specific overexpression of human stem cell factor promotes epicardial activation and arteriogenesis after myocardial infarction.

Author information

1
From the Departments of Physiology and Pharmacology (F.-L.X., Y.L., X.L., D.L.J., Q.F.) and Medicine (D.L.J., Q.F.), and Lawson Health Research Institute (D.L.J., Q.F.), Western University, London, Ontario, Canada.
2
From the Departments of Physiology and Pharmacology (F.-L.X., Y.L., X.L., D.L.J., Q.F.) and Medicine (D.L.J., Q.F.), and Lawson Health Research Institute (D.L.J., Q.F.), Western University, London, Ontario, Canada. qfeng@uwo.ca.

Abstract

BACKGROUND:

The adult epicardium is a potential source of cardiac progenitors after myocardial infarction (MI). We tested the hypothesis that cardiomyocyte-specific overexpression of membrane-associated human stem cell factor (hSCF) enhances epicardial activation, epicardium-derived cells (EPDCs) production, and myocardial arteriogenesis post MI.

METHODS AND RESULTS:

Wild-type and the inducible cardiac-specific hSCF transgenic (hSCF/tetracycline transactivator) mice were subjected to MI. Wilms tumor-1 (Wt1)-positive epicardial cells were higher in hSCF/tetracycline transactivator compared with wild-type mice 3 days post MI. Arteriole density was significantly higher in the peri-infarct area of hSCF/tetracycline transactivator mice compared with wild-type mice 5 days post MI. In cultured EPDCs, adenoviral hSCF treatment significantly increased cell proliferation and growth factor expression. Furthermore, adenoviral hSCF treatment in wild-type cardiomyocytes significantly increased EPDC migration. These effects of hSCF overexpression on EPDC proliferation and growth factor expression were all abrogated by ACK2, a neutralizing antibody against c-kit. Finally, lineage tracing using ROSA(mTmG);Wt1(CreER) mice showed that adenoviral hSCF treatment increased Wt1(+) lineage-derived EPDC migration into the infarcted myocardium 5 days post MI, which was inhibited by ACK2.

CONCLUSIONS:

Cardiomyocyte-specific overexpression of hSCF promotes epicardial activation and myocardial arteriogenesis post MI.

KEYWORDS:

heart failure; myocardial infarction; regeneration; stem cell factor; stem cells

[Indexed for MEDLINE]

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