Progressive Alterations in Microstructural Organization and Biomechanical Response in the ApoE Mouse Model of Aneurysm and the Underlying Changes in Biochemistry

Persistent Link:
http://hdl.handle.net/10150/581126
Title:
Progressive Alterations in Microstructural Organization and Biomechanical Response in the ApoE Mouse Model of Aneurysm and the Underlying Changes in Biochemistry
Author:
Haskett, Darren
Issue Date:
2015
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Abdominal Aortic Aneurysm (AAA) is a complex disease that leads to a localized dilation of the infrarenal aorta that develops over years. Longitudinal information in humans has been difficult to obtain for this disease, therefore mouse models have become increasingly used to study the development of AAAs. The objective of this study was to determine any changes that occur in the biomechanical response and fiber microstructure in the apolipoprotein E difficient (ApoE-/-) angiotensin II (AngII) infused mouse model of aneurysm during disease progression, as well as determine some of the underlying changes in biochemistry, and demonstrate a novel method of reducing any pathogenic protease activity. Using a Microbiaxial Opto-Mechanical Device (MOD), ex vivo studies included adult aortas of ApoE-/- AngII infused mice excised and tested for mechanical response simultaneously imaged using two-photon microscopy to assess the microstructure at multiple time points. In vitro and ex vivo studies have shown changes in protease concentrations with the use of FRET based proteolytic beacons able to provide a non-destructive method to quantify protease activity measured against mechanical and microstructural changes. In vitro studies have demonstrated protease activity can be reduced using a molecule providing a positive feedback mechanism for protease inhibition and possibly provide a reduction in aneurysm progression.
Type:
text; Electronic Dissertation
Keywords:
AAA; ApoE; Biomechanics; MMP; Biomedical Engineering; 2-Photon
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Biomedical Engineering
Degree Grantor:
University of Arizona
Advisor:
Vande Geest, Jonathan P.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleProgressive Alterations in Microstructural Organization and Biomechanical Response in the ApoE Mouse Model of Aneurysm and the Underlying Changes in Biochemistryen_US
dc.creatorHaskett, Darrenen
dc.contributor.authorHaskett, Darrenen
dc.date.issued2015en
dc.publisherThe University of Arizona.en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en
dc.description.abstractAbdominal Aortic Aneurysm (AAA) is a complex disease that leads to a localized dilation of the infrarenal aorta that develops over years. Longitudinal information in humans has been difficult to obtain for this disease, therefore mouse models have become increasingly used to study the development of AAAs. The objective of this study was to determine any changes that occur in the biomechanical response and fiber microstructure in the apolipoprotein E difficient (ApoE-/-) angiotensin II (AngII) infused mouse model of aneurysm during disease progression, as well as determine some of the underlying changes in biochemistry, and demonstrate a novel method of reducing any pathogenic protease activity. Using a Microbiaxial Opto-Mechanical Device (MOD), ex vivo studies included adult aortas of ApoE-/- AngII infused mice excised and tested for mechanical response simultaneously imaged using two-photon microscopy to assess the microstructure at multiple time points. In vitro and ex vivo studies have shown changes in protease concentrations with the use of FRET based proteolytic beacons able to provide a non-destructive method to quantify protease activity measured against mechanical and microstructural changes. In vitro studies have demonstrated protease activity can be reduced using a molecule providing a positive feedback mechanism for protease inhibition and possibly provide a reduction in aneurysm progression.en
dc.typetexten
dc.typeElectronic Dissertationen
dc.subjectAAAen
dc.subjectApoEen
dc.subjectBiomechanicsen
dc.subjectMMPen
dc.subjectBiomedical Engineeringen
dc.subject2-Photonen
thesis.degree.namePh.D.en
thesis.degree.leveldoctoralen
thesis.degree.disciplineGraduate Collegeen
thesis.degree.disciplineBiomedical Engineeringen
thesis.degree.grantorUniversity of Arizonaen
dc.contributor.advisorVande Geest, Jonathan P.en
dc.contributor.committeememberVande Geest, Jonathan P.en
dc.contributor.committeememberIndick, Juliaen
dc.contributor.committeememberMcGrath, Dominicen
dc.contributor.committeememberUtzinger, Ursen
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.