This dissertation project was aimed at elucidating cellular and molecular responses to myocardial infarction. Our work identified canonical wnt signaling as a molecular pathway that is induced in the healing (granulation tissue formation) stages of myocardial infarction (MI). We identified endothelial-to-mesenchymal transition as a cellular response to MI that occurs during granulation tissue formation, coincident with canonical wnt activation. We show that canonical wnt signaling is sufficient to induce endothelial-to-mesenchymal transition in the mature vasculature. Our findings suggest that canonical wnt signaling mediates endothelial-to-mesenchymal transition to generate new blood vessels and scar-forming myofibroblasts during post-infarction granulation tissue formation. These findings suggest an intricate cellular (EndMT) and molecular (canonical wnt signaling) connection between two critical repair mechanisms with apparently opposing effects, beneficial neovascularization and detrimental fibrosis. This intrinsic link may open the opportunity to improve the course of cardiac repair post-MI by temporal and cell type-specific manipulation of canonical wnt signaling.
Approved: Professor Antonis Hatzopoulos Date: 09-02-2010
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-09142010-182027 |
| Date | 21 September 2010 |
| Creators | Aisagbonhi, Omonigho Augustina |
| Contributors | Scott Baldwin, Ethan Lee, Steve Hann, Antonis Hatzopoulos, Al Reynolds |
| 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-09142010-182027/ |
| Rights | unrestricted, 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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