title: Cardiac functional improvement by a human Bcl-2 transgene in a mouse model of ischemia/reperfusion injury.
abstract: BACKGROUND
  Apoptosis has been shown to contribute to myocardial reperfusion injury. It has been suggested that, in reducing the apoptotic component within the ischemic area at risk, Bcl-2 overexpression could lead to a ventricular function improvement.
  
  
  METHODS
  Transgenic mice overexpressing the anti-apoptotic human Bcl-2 cDNA in heart were subjected to a 1-h left coronary artery occlusion followed by a 24-h reperfusion. At the end of the experiment, left ventricular function was assessed by two-dimensional echocardiography. After sacrifice, the area at risk (AR) and the infarct area (IA) were determined by Evans blue and triphenyltetrazolium chloride staining, respectively. The extent of apoptosis was assessed by the TUNEL method. Non-transgenic littermates served as controls.
  
  
  RESULTS
  Baseline AR was not different between Bcl-2 transgenic mice and their wild-type littermates. In contrast, left ventricular ejection fraction was significantly improved in the transgenic mice line (61.25 +/- 4.0%) compared to non-transgenic littermates (43.2 +/- 5.0%, p < 0.01). This functional amelioration was correlated with a significant reduction of infarct size in transgenic animals (IA/AR 18.51 +/- 3.4% vs 50.83 +/- 8.4% in non-transgenic littermates). Finally, apoptotic nuclei were less numerous in transgenic mice than in controls as quantified by TUNEL analysis (8.1 +/- 2.2% vs 20.6 +/- 4.4%).
  
  
  CONCLUSIONS
  Bcl-2 overexpression is effective in reducing myocardial reperfusion injury and improving heart function. This benefit correlates with a reduction of cardiomyocyte apoptosis. The apoptotic component of ischemia/reperfusion injury could therefore constitute a new therapeutic target in the acute phase of myocardial infarction.
authors.affiliation: U.129 INSERM, ICGM, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Brocheriou
authors.forename: A A
authors.initials: AA
authors.lastname: Hagège
authors.forename: A
authors.initials: A
authors.lastname: Oubenaïssa
authors.forename: M
authors.initials: M
authors.lastname: Lambert
authors.forename: V O
authors.initials: VO
authors.lastname: Mallet
authors.forename: M
authors.initials: M
authors.lastname: Duriez
authors.forename: M
authors.initials: M
authors.lastname: Wassef
authors.forename: A
authors.initials: A
authors.lastname: Kahn
authors.forename: P
authors.initials: P
authors.lastname: Menasché
authors.forename: H
authors.initials: H
authors.lastname: Gilgenkrantz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004195:Disease Models, Animal; D004452:Echocardiography; D015870:Gene Expression; D019254:Genes, bcl-2; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000628:therapy; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D016277:Ventricular Function, Left