Date of Graduation

5-2019

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering (MSBME)

Degree Level

Graduate

Department

Biomedical Engineering

Advisor

Kartik Balachandran

Committee Member

Jeffrey Wolchok

Second Committee Member

Hannah Jensen

Third Committee Member

Adrian Chester

Keywords

Angiotensin-II, Aortic valve stenosis, Renin angiotensin signaling, Valve Biomechanics

Abstract

Angiotensin-II (Ang-II), a peptide hormone, is a potent vasoconstrictor and cell mitogen. It has been implicated in the development of hypertension as well as atherosclerosis. Recent work has shown that sclerotic aortic valves possess expression of angiotensin type I receptor (AT-1R) and angiotensin converting enzyme (ACE), suggesting altered angiotensin signaling during disease. The role of altered angiotensin signaling on aortic valve mechanics, however, is not clearly understood. We seek to understand the direct effects of the renin angiotensin signaling (RAS) system on the biological and biomechanical properties of aortic valve tissue and develop a finite constitutive model that mimics the effects of RAS on aortic valves. Our results showed that the mechanical properties such as stiffness were altered by RAS mediators. Three phenomenological constitutive models were utilize to characterize the biomechanical changes that occur due to RAS mediators on aortic valves, and the Fung-type model was shown to be the best fit model for the experimental data. Tissue maintained in anisotropy behavior, but the cross-coupling of the fibers was affected. Immunohistochemistry (IHC) showed that RAS affects the phenotypic properties of the cells in the aortic valve tissues. Picrosirius red (PSR) staining suggests that RAS mediators affect the production of collagen fibers, and quantitative polarized light imaging (QPLI) demonstrated that RAS mediators affect the orientation of collagen fibers. We concluded that RAS mediators affected the biological and mechanical functions of the aortic valve leaflet. The activation of VICS and increased production and disorganization of collagen fibers correlated to the stiffness of the tissue. These are all hallmarks of early disease progression, and in the future, we will further investigate the effects of RAS mediators in mechanics of the valve leaflet at the cellular level.

Available for download on Thursday, June 03, 2021

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