title: Cardiac-specific expression of the hepatocyte growth factor (HGF) under the control of a TnIc promoter confers a heart protective effect after myocardial infarction (MI).
abstract: OBJECTIVE
  Uncontrolled therapeutic gene expression and neovascularization in non-specific tissues has lowered the safety of gene therapy. The aim of the study was to identify a cardiac-specific promoter to control target gene expression in heart tissue in vitro and in vivo.
  
  
  METHODS
  Adenovirus vectors containing the firefly luciferase or hepatocyte growth factor (HGF) genes under control of the Troponin I (TnIc) or Cytomegalievirus (CMV) promoters were transfected into cell lines or injected into the left ventricular wall of Sprague Dawley (SD) rats via thoracotomy. Myocardial infarction (MI) was induced immediately before direct injection. In vivo luciferase expression was assessed using a bioluminescence imaging system. Heart function was monitored via echocardiograph intermittently for eight weeks after injection.
  
  
  RESULTS
  The constitutively active CMV promoter yielded luciferase expression throughout the body while luciferase expression driven by the TnIc promoter was largely restricted to the hypoxic heart. The CMV promoter was more efficient, yielding 100-1000 fold more light output than the TnIc promoter. Four weeks after injection, we observed a significant decline in the ejection fraction (EF) in saline and Ad-Null groups but a 17% increase in the Ad-CMV-HGF group. No change in EF was observed in the Ad-TnIc-HGF group.
  
  
  CONCLUSIONS
  The adenovirus vector combined with the TnIc promoter largely restricts gene-targeted therapy in the hypoxic heart and prevents heart failure after myocardial infarction.
authors: Zhihui
authors: Z
authors: Xu
authors: Zhengxian
authors: Z
authors: Tao
authors: Zhuowen
authors: Z
authors: Xu
authors: Yuefeng
authors: Y
authors: Yang
authors: Hua
authors: H
authors: Wang
authors: Lisheng
authors: L
authors: Wang
authors: Zuze
authors: Z
authors: Wu
authors: Qi
authors: Q
authors: Tan
authors: Ningtian
authors: N
authors: Zhou
authors: Ming
authors: M
authors: Zhang
authors: Pengsheng
authors: P
authors: Chen
authors: Department of Cardiology and Department of Geriatrics, The First affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China. zhijianyangnj@njmu.edu.cn.
authors: Zhijian
authors: Z
authors: Yang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D006352:Heart Ventricles / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000627:therapeutic use; D006801:Humans; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D011401:Promoter Regions, Genetic; D051381:Rats; D013908:Thoracotomy; D019210:Troponin I / Q000235:genetics
chemical_list: D019210:Troponin I; D017228:Hepatocyte Growth Factor