Date of Award

Spring 2021

Document Type

Open Access Dissertation

Department

Biomedical Engineering

First Advisor

Tarek M. Shazly

Abstract

Vascular endothelial cell dysfunction (ECD) is a disease characterized by the inability of the vascular endothelial cells to transmit signaling molecules, namely nitric oxide (NO), in response to changes in blood flow rate. This disease is shown to be incident in the onset of more severe vascular disease such as hypertension, atherosclerosis, and heart failure. Long-term ECD is shown to cause long-term remodeling such as decreased flow-mediated dilation, increased pulse-wave velocity, intimal-medial thickening, and increased wall stiffness due to collagen deposition. We used second harmonic generation (SHG) microscopy to analyze this change in the collagen microstructure of the arterial extracellular matrix due to decreased nitric oxide signaling. In the analysis of these microscopic images, we observed a significant increase in the relative frequency of circumferentially oriented collagen fibers with age in knockout mice with an expected decrease in NO signaling compared to their wild-type counterparts. Within these mouse arteries, we also observed a sharper decrease in the tortuosity of the circumferential fibers compared to the axial fibers. Overall, these results have implications toward studies in NO-dependent stress-mediated remodeling and future computational modeling efforts of ECD.

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