Graduate Studies
First Advisor
Ryan M. Pedrigi
Date of this Version
4-2024
Document Type
Article
Citation
A thesis presented to the faculty of the Graduate College at the University of Nebraska in partial fulfillment of requirements for the degree of Master of Science
Major: Biochemistry
Under the supervision of Professor Ryan M. Pedrigi
Lincoln, Nebraska, April 2024
Abstract
The endothelium is the central regulator of all classically understood functions of the vasculature. Decades of research has established that mechanical cues from the blood flow environment induce substantial effects on cell phenotype, and initiate deadly diseases such as atherosclerosis. Our recent work demonstrated that mechanical stimuli like shear stress can be therapeutic against disease progression most likely through renormalization of a dysfunctional endothelium. This finding motivates the development of therapies that can leverage the health promoting effects of mechanical stimuli on the endothelium. For nearly 20 years, ultrasound has been used to deliver mechanical stimuli to tissues and the endothelium for therapeutic effect, though little is understood of what sonication parameters maximize this response. Herein, we address this challenge by demonstrating that endothelial cells exposed to low intensity pulsed ultrasound (LIPUS) for longer durations than previously explored exhibit temporally dependent expression of endothelial nitric oxide synthase (eNOS) and increased cell density compared to static controls. We further demonstrate that this response is dependent upon the generation of a stable in-plane pressure field derived from incoming and reflecting wave interactions. Additionally, we show that pulse frequency affects the response of endothelial cells to ultrasound and can induce cell alignment. Ultimately, this work improves our understanding of the beneficial effects of LIPUS on the endothelium by establishing the link between cell proliferation and eNOS expression that is derived from acoustic pressure fields.
Advisor: Ryan M. Pedrigi
Comments
Copyright 2024, Ian McCue. Used by permission