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Left Ventricular Unloading After Acute Myocardial Infarction Reduces MMP/JNK Associated Apoptosis and Promotes FAK Cell-Survival Signaling.
- Source :
-
The Annals of thoracic surgery [Ann Thorac Surg] 2016 Dec; Vol. 102 (6), pp. 1919-1924. Date of Electronic Publication: 2016 Jul 01. - Publication Year :
- 2016
-
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.<br />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.<br />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.<br />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.<br /> (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Apoptosis
Disease Models, Animal
In Situ Nick-End Labeling
Male
Myocardial Infarction therapy
Myocardium enzymology
Phosphorylation
Protein Processing, Post-Translational
Sheep
Stress, Mechanical
Focal Adhesion Protein-Tyrosine Kinases physiology
Heart Ventricles physiopathology
Heart-Assist Devices
JNK Mitogen-Activated Protein Kinases physiology
Matrix Metalloproteinase 2 physiology
Myocardial Infarction physiopathology
Signal Transduction
Ventricular Remodeling physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1552-6259
- Volume :
- 102
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Annals of thoracic surgery
- Publication Type :
- Academic Journal
- Accession number :
- 27378553
- Full Text :
- https://doi.org/10.1016/j.athoracsur.2016.05.007