title: Regional imbalanced activation of the calcineurin/BAD apoptotic pathway and the PI3K/Akt survival pathway after myocardial infarction.
abstract: BACKGROUND
  The underlying molecular mechanisms of the remodeling after myocardial infarction (MI) remain unclear. The purpose of this study was to investigate the role of a survival pathway (PI3K/Akt) and an apoptosis pathway (calcineurin/BAD) in the remodeling after MI in a large animal model.
  
  
  METHODS
  Ten Dorset hybrid sheep underwent 25% MI in the left ventricle (LV, n=10). Five sheep were used as sham control. The regional strain was calculated from sonomicrometry. Apoptosis and the activation of the PI3K/Akt and calcineurin/BAD pathways were evaluated in the non-ischemic adjacent zone and the remote zone relative to infarct by immunoblotting, immunoprecipitation, and immunofluorescence staining.
  
  
  RESULTS
  Dilation and dysfunction of LV were present at 12 weeks after MI. The regional strain in the adjacent zone was significantly higher than in the remote zone at 12 weeks (36.6 ± 4.0% vs 9.5 ± 3.6%, p<0.05). Apoptosis was more severe in the adjacent zone than in the remote zone. The PI3K/Akt and calcineurin/BAD pathways were activated in the adjacent zone. Dephosphorylation and translocation of BAD were evident in the adjacent zone. Regional correlation between the strain and the expression of calcineurin/BAD indicated that the activation was strain-related (R(2)=0.46, 0.48, 0.39 for calcineurin, BAD, mitochondrial BAD, respectively, p<0.05).
  
  
  CONCLUSIONS
  The PI3K/Akt survival and calcineurin/BAD apoptotic pathways were concomitantly activated in the non-ischemic adjacent zone after MI. The calcineurin/BAD pathway is strain related and its imbalanced activation may be one of the causes of progressive remodeling after MI.
authors.affiliation: Departments of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Tieluo
authors.initials: T
authors.lastname: Li
authors.forename: Ahmet
authors.initials: A
authors.lastname: Kilic
authors.forename: Xufeng
authors.initials: X
authors.lastname: Wei
authors.forename: Changfu
authors.initials: C
authors.lastname: Wu
authors.forename: Gary
authors.initials: G
authors.lastname: Schwartzbauer
authors.forename: G Kwame
authors.initials: GK
authors.lastname: Yankey
authors.forename: Christopher
authors.initials: C
authors.lastname: DeFilippi
authors.forename: Meredith
authors.initials: M
authors.lastname: Bond
authors.forename: Zhongjun J
authors.initials: ZJ
authors.lastname: Wu
authors.forename: Bartley P
authors.initials: BP
authors.lastname: Griffith
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019703:Calcineurin / Q000378:metabolism* / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism* / Q000502:physiology; D012756:Sheep; D015398:Signal Transduction / Q000502:physiology; D051025:bcl-Associated Death Protein / Q000378:metabolism* / Q000502:physiology
chemical_list: D051025:bcl-Associated Death Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019703:Calcineurin
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