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Title page for ETD etd-12042015-110956

Type of Document Dissertation
Author Paik, David Tohyun
Author's Email Address david.t.paik@vanderbilt.edu
URN etd-12042015-110956
Title Canonical Wnt signaling activation enhances cardiac tissue repair by arteriole formation and attenuation of fibrosis
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
H. Scott Baldwin Committee Chair
Antonis K. Hatzopoulos Committee Member
David M. Miller, III Committee Member
Mark P. deCaestecker Committee Member
Stephen R. Hann Committee Member
  • fibrosis
  • Cardiac repair
  • Wnt10b
  • neovascularization
  • Wnt signaling
  • Myocardial infarction
Date of Defense 2015-11-12
Availability unrestricted
Myocardial infarction (MI) causes irreversible tissue damage, leading to heart failure. Our laboratory found canonical Wnt signaling and the Wnt10b ligand are strongly induced in mouse and human hearts after MI. Wnt10b regulates cell fate in various organs, yet its role in the heart is unknown. To investigate the effects of Wnt10b gain-of-function on cardiac repair mechanisms and functional outcomes after injury, we generated αMHC-Wnt10b transgenic (TG) mouse line that overexpresses Wnt10b in adult cardiomyocytes. Following acute myocardial injury, the TG mice displayed improved recovery of cardiac function, accompanied by enhanced neovascularization and attenuated scar fibrosis. Wnt10b stimulated expression of vascular endothelial growth factor receptor 2 in endothelial cells and angiopoietin-1 in vascular smooth muscle cells through nuclear factor-κB activation to promote stabilized blood vessel formation. Wnt10b also reduced the number of myofibroblasts to mitigate fibrosis. My findings may lead to novel strategies to optimize the inherent repair capacity of the heart and prevent the onset of heart failure.
  Filename       Size       Approximate Download Time (Hours:Minutes:Seconds) 
 28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access 
  Paik.pdf 4.63 Mb 00:21:26 00:11:01 00:09:39 00:04:49 00:00:24

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