title: Cardiac-specific overexpression of human stem cell factor promotes epicardial activation and arteriogenesis after myocardial infarction.
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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Fu-Li
authors.initials: FL
authors.lastname: Xiang
authors.affiliation: 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.
authors.forename: Yin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Xiangru
authors.initials: X
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Jones
authors.affiliation: 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.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Feng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D010496:Pericardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D019089:Stem Cell Factor
keywords: heart failure; myocardial infarction; regeneration; stem cell factor; stem cells