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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12042015-110956 |
| Date | 04 December 2015 |
| Creators | Paik, David Tohyun |
| Contributors | Stephen R. Hann, David M. Miller, III, Mark P. deCaestecker, Antonis K. Hatzopoulos, H. Scott Baldwin |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-12042015-110956/ |
| Rights | restrictone, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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