Left Ventricular Unloading After Acute Myocardial Infarction Reduces MMP/JNK Associated Apoptosis and Promotes FAK Cell-Survival Signaling

Tieluo Li, Xufeng Wei, Charles F. Evans, Pablo G. Sanchez, Shuying Li, Zhongjun J. Wu, Bartley P. Griffith

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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.

Original languageEnglish (US)
Pages (from-to)1919-1924
Number of pages6
JournalAnnals of Thoracic Surgery
Volume102
Issue number6
DOIs
Publication statusPublished - Dec 1 2016

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All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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