Engineered Early Embryonic Cardiac Tissue Increases Cardiomyocyte Proliferation by Cyclic Mechanical Stretch via p38-MAP Kinase Phosphorylation
- 1 June 2009
- journal article
- research article
- Published by Mary Ann Liebert Inc in Tissue Engineering, Part A
- Vol. 15 (6), 1373-1380
- https://doi.org/10.1089/ten.tea.2008.0169
Abstract
Cardiomyocyte (CM) transplantation is one therapeutic option for cardiac repair. Studies suggest that fetal CMs display the best cell type for cardiac repair, which can finitely proliferate, integrate with injured host myocardium, and restore cardiac function. We have recently developed an engineered early embryonic cardiac tissue (EEECT) using embryonic cardiac cells and have shown that EEECT contractile properties and cellular proliferative response to cyclic mechanical stretch stimulation mimic developing fetal myocardium. However, it remains unknown whether cyclic mechanical stretch–mediated high cellular proliferation activity within EEECT reflects CM or non-CM population. Studies have shown that p38-mitogen-activated protein kinase (p38MAPK) plays an important role in both cyclic mechanical stretch stimulation and cellular proliferation. Therefore, in the present study, we tested the hypothesis that cyclic mechanical stretch (0.5 Hz, 5% strain for 48 h) specifically increases EEECT CM proliferation mediated by p38MAPK activity. Cyclic mechanical stretch increased CM, but not non-CM, proliferation and increased p38MAPK phosphorylation. Treatment of EEECT with the p38MAPK inhibitor, SB202190, reduced CM proliferation. The negative CM proliferation effects of SB202190 were not reversed by concurrent stretch stimulation. Results suggest that immature CM proliferation within EEECT can be positively regulated by mechanical stretch and negatively regulated by p38MAPK inhibition.Keywords
This publication has 58 references indexed in Scilit:
- Regulation of the Na+/Ca2+ exchanger (NCX) in the murine embryonic heartCardiovascular Research, 2007
- Cardiac Myocyte Cell Cycle Control in Development, Disease, and RegenerationPhysiological Reviews, 2007
- Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune responseThe FASEB Journal, 2007
- Akt Promotes Increased Cardiomyocyte Cycling and Expansion of the Cardiac Progenitor Cell PopulationCirculation Research, 2006
- p38 Kinase rescues failing myocardium after myocardial infarction: evidence for angiogenic and anti‐apoptotic mechanismsThe FASEB Journal, 2006
- Myostatin Regulates Cardiomyocyte Growth Through Modulation of Akt SignalingCirculation Research, 2006
- p38 Mitogen‐Activated Protein Kinase Activity Commits Embryonic Stem Cells to Either Neurogenesis or CardiomyogenesisThe International Journal of Cell Cloning, 2006
- Mitogen-activated protein kinase activation and regulation in the pressure-loaded fetal ovine heartAmerican Journal of Physiology-Heart and Circulatory Physiology, 2006
- The Regulation and Activities of the Multifunctional Serine/Threonine Kinase Akt/PKBExperimental Cell Research, 1999
- Age-dependent changes in expression of alpha1-adrenergic receptors in rat myocardiumBiochemical and Biophysical Research Communications, 1986