title: Deterioration of cardiac function after acute myocardial infarction is prevented by transplantation of modified endothelial progenitor cells overexpressing endothelial NO synthases.
abstract: OBJECTIVE
  Stem cell transplantation and gene therapies have been shown to attenuate myocardial dysfunction after myocardial infarction (AMI) in different acute and chronic animal models. The aim of this study was to assess the potential therapeutic efficacy of endothelial NO synthases (eNOS)-expressing endothelial progenitor cells (EPCs) on infarcted hearts.
  
  
  METHODS
  Lentiviral eNOS-infected EPCs were injected after 1 h of ligation of the left anterior descending artery (LAD). The pro-inflammatory cytokines TNF-α and IL-1β levels in cardiac tissue were measured by ELISA at 3 days after transplantation. 28 days post AMI (before sacrifice), Left ventricular function of each group was determined by echocardiography and pressure-volume system. Cardiac tissues were analyzed with hematoxylin and eosin (H&E) staining and immunohistochemisty. eNOS expression in cardiac tissues was detected by western blot, and NO production of cardiac tissues was determined using an NO assay kit.
  
  
  RESULTS
  TNF-α and IL-1β levels in cardiac tissue were decreased significantly at 3 days after transplantation of lentiviral with eNOS infected EPCs compared to medium control, eNOS lentiviral vector and normal EPCs. At the 28 day after AMI, echocardiography and hemodynamic measurements, and isolated heart studies showed great therapeutic efficacy in improvement of cardiac function, reduction of infarcted size and improvement of vascular densities in the peri-infarct region after intramyocardial application of lentiviral eNOS-infected EPCs compared to medium control, eNOS lentiviral vector and normal EPCs. The eNOS over-expression in cardiac tissue was observed in the eNOS-EPCs and eNOS lentiviral vector group, and NO levels were increased significantly in the eNOS-EPCs and eNOS lentiviral vector group compared to the other three groups (sham operated group, transplantation of medium or EPCs group).
  
  
  CONCLUSIONS
  EPCs can be an attractive vehicle for the exogenous eNOS expression into heart after infarction, which is beneficial to prevent deterioration and promote restoration of cardiac function after AMI by improving angiogenesis.
authors.affiliation: Departments of Cardiology, ChangHai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Mingbiao
authors.initials: M
authors.lastname: Gu
authors.forename: Xianxian
authors.initials: X
authors.lastname: Zhao
authors.forename: Xing
authors.initials: X
authors.lastname: Zheng
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Qin
authors.forename: Xiaohua
authors.initials: X
authors.lastname: You
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004452:Echocardiography; D042783:Endothelial Cells / Q000166:cytology*; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III