Atherosclerosis is a chronic vascular disease which is the underlying cause of over half the deaths in the United States each year. Variations in local vascular hemodynamics predispose select sites in the vasculature to atherosclerosis and the atherosclerotic lesions, in turn, alter the biomechanical functioning of the local microenvironment, the consequences of which are not well understood on a molecular level. Work from our lab demonstrated that the small proline rich repeat protein 3 (SPRR3), which is known to be biomechanically responsive in stratified epithelia, is selectively expressed in vascular smooth muscle cells (VSMCs) in the atherosclerotic microenvironment. SPRR3 has stable head and tail domains that contain amino acid domains which are substrates for transglutaminase. Additionally, SPRR3 has a highly flexible, proline-rich central domain that is believed to confer elasticity. We have shown that in VSMCs, SPRR3 transcripts are upregulated by prolonged cyclic strain, as sensed through integrin α1β1 integrin binding to type I collagen. Furthermore, we have shown that SPRR3 overexpression in VSMCs promotes migration and inhibits contraction, though this effect is independent of transglutamination of the protein. Ongoing and future work will demonstrate a role for SPRR3 in signaling pathways, such as in the Akt pathway. Ultimately, the study of SPRR3 will provide insight into the molecular pathogenesis of atherosclerosis.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03242009-105847 |
| Date | 02 April 2009 |
| Creators | Pyle, Amy Lauren |
| Contributors | Jeffery M. Davidson, Samuel A. Santoro, Richard L. Hoover, Jin Chen, Jeff Reese |
| 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-03242009-105847/ |
| 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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