title: Left Ventricular Unloading After Acute Myocardial Infarction Reduces MMP/JNK Associated Apoptosis and Promotes FAK Cell-Survival Signaling.
abstract: BACKGROUND
  The mechanism underlying left ventricular remodeling and reverse remodeling in the setting of mechanical support following acute myocardial infarction (MI) is unclear. We tested the hypothesis that left ventricular assist device (LVAD) unloading can decrease apoptotic signals after MI.
  
  
  METHODS
  An MI model was created in 16 sheep by coronary artery ligation. Eight were unloaded with a LVAD during the first 2 weeks after MI and observed for 10 more weeks. Myocardial tissue was collected from the nonischemic adjacent zone and the remote zone. Proteins in the apoptotic matrix metalloproteinases (MMPs)-2/c-Jun N-terminal kinase (JNK) and prosurvival β1D-integrin/focal adhesion kinase (FAK) pathway were quantified.
  
  
  RESULTS
  Increased TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) positive nuclei were observed in the MI group and to a lesser extent in the LVAD group (6.18 ± 0.26 versus 0.82 ± 0.18; p < 0.05). Pro-MMP-2, MMP-2, JNK, and phosphorylated (p)-JNK were all elevated in the adjacent zone of the MI-only group but not in the adjacent zone of the LVAD-supported group. There were higher levels of prosurvival p-FAK in the LVAD-supported group than in the MI group.
  
  
  CONCLUSIONS
  MMP-2/JNK apoptotic and β1D-integrin/FAK survival pathways are activated in the nonischemic adjacent zone after MI in adult sheep. LVAD unloading of approximately 50% cardiac output for 2 weeks attenuates remodeling in part by its negative effect on stretch-induced apoptosis and inhibition of MMP-2 activity.
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Tieluo
authors.initials: T
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Wei
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Evans
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Pablo G
authors.initials: PG
authors.lastname: Sanchez
authors.affiliation: Division of Cardiology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Shuying
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiovascular and Thoracic Surgery; University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Zhongjun J
authors.initials: ZJ
authors.lastname: Wu
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland. Electronic address: bgriffith@smail.umaryland.edu.
authors.forename: Bartley P
authors.initials: BP
authors.lastname: Griffith
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology*; D006352:Heart Ventricles / Q000503:physiopathology*; D006353:Heart-Assist Devices; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000628:therapy; D009206:Myocardium / Q000201:enzymology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012756:Sheep; D015398:Signal Transduction; D013314:Stress, Mechanical; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2