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University of Louisville

1. Salabei, Joshua Kuimeta. Regulation of vascular smooth muscle cell phenotype.

Degree: PhD, 2012, University of Louisville

Vascular injury and chronic arterial diseases such as atherosclerosis and restenosis result in exposure of vascular smooth muscle cells (VSMCs) to increased concentrations of growth factors triggering a change from a contractile to a synthetic phenotype. The mechanisms by which growth factors trigger VSMC phenotype transitions remain unclear. Because phenotype switching involves the removal of contractile proteins, we hypothesized that autophagy is an essential modulator of VSMC phenotype. Also, the conversion to the synthetic phenotype is accompanied by cellular changes that trigger metabolic changes to meet the increasing demands for cellular energy. Little is known however about the contributions of different substrates metabolized for energy production and how these metabolic changes integrate with phenotype switching and VSMC proliferation. We further hypothesize that metabolic changes induced by PDGF are required for phenotype switching and proliferation. Studies presented here show that: 1) Treatment of VSMCs with platelet-derived growth factor PDGF-BB results in activation of autophagy which is required for degradation of contractile proteins during phenotype switching; 2) Increased glycolytic flux caused by PDGF treatment is required for expression of the synthetic cytokine osteopontin and for proliferation; and 3) Mitochondria fragmentation and increased fatty acid oxidation are required for PDGF-induced VSMC proliferation. These results support the overall hypothesis that autophagy and changes in intermediary metabolic pathways are modulators of PDGF-induced phenotype transition. Our findings suggest that autophagy-directed therapies may provide effective treatments against vascular diseases such as atherosclerosis and restenosis. Advisors/Committee Members: Bhatnagar, Aruni.

Subjects/Keywords: Cardiovascular; vascular smooth muscle; phenotype; PDGF autophagy; O-GlcNAc

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Salabei, J. K. (2012). Regulation of vascular smooth muscle cell phenotype. (Doctoral Dissertation). University of Louisville. Retrieved from 10.18297/etd/1250 ; https://ir.library.louisville.edu/etd/1250

Chicago Manual of Style (16th Edition):

Salabei, Joshua Kuimeta. “Regulation of vascular smooth muscle cell phenotype.” 2012. Doctoral Dissertation, University of Louisville. Accessed September 23, 2019. 10.18297/etd/1250 ; https://ir.library.louisville.edu/etd/1250.

MLA Handbook (7th Edition):

Salabei, Joshua Kuimeta. “Regulation of vascular smooth muscle cell phenotype.” 2012. Web. 23 Sep 2019.

Vancouver:

Salabei JK. Regulation of vascular smooth muscle cell phenotype. [Internet] [Doctoral dissertation]. University of Louisville; 2012. [cited 2019 Sep 23]. Available from: 10.18297/etd/1250 ; https://ir.library.louisville.edu/etd/1250.

Council of Science Editors:

Salabei JK. Regulation of vascular smooth muscle cell phenotype. [Doctoral Dissertation]. University of Louisville; 2012. Available from: 10.18297/etd/1250 ; https://ir.library.louisville.edu/etd/1250

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