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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Cell Proliferation
  • Cells, Cultured
  • Coronary Vessels / metabolism*
  • Coronary Vessels / pathology
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental*
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Neovascularization, Pathologic
  • Pericardium / metabolism*
  • Pericardium / pathology
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction
  • Stem Cell Factor / biosynthesis
  • Stem Cell Factor / genetics*


  • RNA, Messenger
  • Stem Cell Factor