BioE Ph.D. Proposal

January 17, 2024

11:00 AM

Location: E-160 HSRB I, Emory University

Zoom Link: https://gatech.zoom.us/j/94000206297

Committee:

Luke Brewster, M.D., Ph.D. (Ph.D. Advisor)  (Vascular Surgery, Emory University)

Hanjoong Jo, Ph.D. (Biomedical Engineering, Emory and GT)

Rudolph Gleason, Ph.D.  (Biomedical Engineering and Mechanical Engineering, GT)

Michael Walsh, Ph.D. (Biomedical Engineering, University of Limerick)

Brian Aguado, Ph.D. (Bioengineering, University of California San Diego)

Effect of Artery Type and Function on Atherosclerotic Plaque Progression and Phenotype

Arteries are classified as elastic or muscular. Elastic arteries, like the carotid artery (CA), store elastic energy during systole while muscular arteries, like the femoral artery (FA), regulate blood flow to peripheral organs. Interestingly, atherosclerotic plaque composition varies with artery type; elastic arteries develop lipid-rich plaque and muscular arteries develop fibrotic plaque. Arterial remodeling is a complex process involving arterial stiffening and atherosclerotic plaque formation. Atherosclerosis is characterized by the deposition of plaque at locations of disturbed blood flow (d-flow). Endothelial cells (ECs) sense d-flow and stiffness leading to EC dysfunction, fibroinflammatory pathway activation, and inwards remodeling of the artery. The goal of this proposal is to better understand how the mechanical stiffness and fluid dynamic profiles of the elastic CAs and muscular FAs lead to distinct atherosclerotic plaque formation. Differences across biological sex will also be evaluated. Murine models of partial ligation in the CAs and FAs will be used to induce d-flow conditions and fibulin-5 knockout mice will be used to induce arterial stiffening. Innovative tools in transcriptomics and established tests in biomechanics will be used to characterize atherosclerosis progression. Finally, a 1D fluid-solid-growth-remodeling computational model will be developed to predict changes in the hemodynamic profiles, geometries, and biomechanical properties of the arteries as atherosclerosis progresses taking into consideration the differences found due to artery type and arterial stiffness.