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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Advisor: Hanjoong Jo, Ph.D. (Georgia Institute of Technology & Emory University)
Committee:
Michael Davis, Ph.D. (Georgia Institute of Technology & Emory University)
Charles Searles Jr., M.D. (Emory School of Medicine)
Loren Williams, Ph.D. (Georgia Institute of Technology)
Younan Xia, Ph.D. (Georgia Institute of Technology)
miR-744 Modulation by Disturbed Flow and Role in Endothelial Dysfunction and Atherosclerosis
Atherosclerosis is the leading cause of death worldwide despite the use of cholesterol-lowering statins and anti-platelet drugs. The disease localizes to arterial regions exposed to disturbed flow due to the effect of low-magnitude and oscillating shear stress (OS) on endothelial gene expression. However, there are no treatment options to target hemodynamic-mediated mechanisms due to a lack of mechanistic understanding. The objective of this proposal is to elucidate the effects of d-flow-induced miRNAs on endothelial gene expression and the mechanisms initiating endothelial dysfunction and atherosclerosis. Recently, our lab reported that miR-663 is highly upregulated by OS in human endothelial cells and potentially induces endothelial inflammation. Interestingly, preliminary studies indicate that another miR-663 family member, miR-744, which has a common seed sequence with miR-663, is also upregulated by OS, and may also induce inflammation. Therefore, the overall hypothesis is that overexpression of miR-744 by OS causes endothelial dysfunction and atherosclerosis. To test the hypothesis, miR-744 modulation of OS-induced endothelial dysfunction will be assessed in vitro, the therapeutic effect of miR-744 inhibition on atherosclerosis development will be assessed in vivo, and relevant direct targets will be determined.
