Rachel Simmons

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1 year 11 months
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disturbed flow and miR-744 in atherosclerosis, anti-miRNA delivery


BSE,Chemical and Biomolecular Engineering, Tulane University, 2011 BS, Cell and Molecular Biology, Tulane University, 2011

Thesis Project Title
miR-744 Modulation by Disturbed Flow and Role in Endothelial Dysfunction and Atherosclerosis
Thesis Project Description

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 (d-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 primate-specific miR-663 is highly upregulated by OS in human endothelial cells and potentially induces endothelial inflammation. Interestingly, preliminary studies indicate that a broadly conserved miRNA, 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

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