title: Cardiomyocyte-specific overexpression of human stem cell factor improves cardiac function and survival after myocardial infarction in mice.
abstract: BACKGROUND
  Soluble stem cell factor (SCF) has been shown to mobilize bone marrow stem cells and improve cardiac repair after myocardial infarction (MI). However, the effect of membrane-associated SCF on cardiac remodeling after MI is not known. The present study investigated the effects of cardiomyocyte-specific overexpression of the membrane-associated isoform of human SCF (hSCF) on cardiac function after MI.
  
  
  RESULTS
  A novel mouse model with tetracycline-inducible and cardiac-specific overexpression of membrane-associated hSCF was generated. MI was induced by left coronary artery ligation. Thirty-day mortality after MI was decreased in hSCF/tetracycline transactivator (tTA) compared with wild-type mice. In vivo cardiac function was significantly improved in hSCF/tTA mice at 5 and 30 days after MI compared with wild-type mice. Endothelial progenitor cell recruitment and capillary density were increased and myocardial apoptosis was decreased in the peri-infarct area of hSCF/tTA mice. Myocyte size was decreased in hSCF/tTA mice 30 days after MI compared with WT mice. Furthermore, hSCF overexpression promoted de novo angiogenesis as assessed by matrigel implantation into the left ventricular myocardium.
  
  
  CONCLUSIONS
  Cardiomyocyte-specific overexpression of hSCF improves myocardial function and survival after MI. These beneficial effects of hSCF may result from increases in endothelial progenitor cell recruitment and neovascularization and decreases in myocardial apoptosis and cardiac remodeling.
authors.affiliation: Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Fu-Li
authors.initials: FL
authors.lastname: Xiang
authors.forename: Xiangru
authors.initials: X
authors.lastname: Lu
authors.forename: Lamis
authors.initials: L
authors.lastname: Hammoud
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Peter
authors.initials: P
authors.lastname: Chidiac
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Robbins
authors.forename: Qingping
authors.initials: Q
authors.lastname: Feng
mesh_terms: D000818:Animals; D017209:Apoptosis; D004318:Doxycycline / Q000494:pharmacology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology; D019089:Stem Cell Factor / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D013752:Tetracycline / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000502:physiology; D016277:Ventricular Function, Left
chemical_list: D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D040301:Vascular Endothelial Growth Factor Receptor-2; D013752:Tetracycline; D004318:Doxycycline