Role of Hydrogen Peroxide in the Development of Abdominal Aortic Aneurysms Open Access

Clark, John Brian (2011)

Permanent URL: https://etd.library.emory.edu/concern/etds/cn69m4331?locale=en
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Abstract


Abstract
Role of Hydrogen Peroxide in the Development of Abdominal Aortic Aneurysms
By John Brian Clark
Abdominal Aortic Aneurysms (AAA) are a significant health problem in the United
States and abroad. In men over the age of 55 it is estimated that the prevalence is between 5-
9%. AAA rupture leads to thousands of deaths each year and is a leading cause of death in
older men. Despite the significant clinical endpoints, very little is known about the initial
events leading to the development of abdominal aortic aneurysms. The hallmarks of AAA
are aortic diameters >50% normal, chronic inflammation of the abdominal aorta, matrix
metalloproteinase (MMP) expression and elastin fragmentation. Many studies suggest a
critical role for reactive oxygen species and oxidative stress in AAA development. The
central hypothesis of this thesis is that a particular reactive oxygen species, hydrogen
peroxide, plays a critical role in the development of AAA. To test this hypothesis we utilized
several different murine models of AAA, ultrasound imaging to monitor aortic dilation, and
Amplex Red to measure relative levels of hydrogen peroxide. Herein, we demonstrate that
increases in hydrogen peroxide levels may be model dependent and commercially available
antioxidant therapies fail to significantly lower hydrogen peroxide levels and have no effect
on AAA development.


Role of Hydrogen Peroxide in the Development of Abdominal Aortic Aneurysms
By
John Brian Clark
B.S., University of Alabama, 2008
Advisor: W. Robert Taylor, M.D., Ph.D.
A thesis submitted to the Faculty of the
James T. Laney School of Graduate Studies of Emory University
in partial fulfillment of the requirements for the degree of
Master of Science in the Division of Biological and Biomedical Sciences
Molecular and Systems Pharmacology
2010

Table of Contents

Table of Contents Chapter 1: General Introduction……………….………...............................……………………..…...1-15

Clinical Significance of Abdominal Aortic Aneurysm…….......................................…………………….…….1-5

Pathophysiology of Abdominal Aortic Aneurysms………………........................................…………………..6-9

Animal Models of Abdominal Aortic Aneurysms……………..........................................…………………...…9-10

Oxidative Stress in Cardiovascular Disease and AAA..…………......................................……….………….11-15

Chapter 2: Calcium Chloride stimulates hydrogen peroxide production and AAA……………..16-25

Introduction …………………………………………………………….........................................................……………16

Materials and Methods…………………………………………...................................................………….….………16-19

Results ………………………………………………………………...........................................................….……………19-20

Conclusions ……………………………………………………….......................................................………….…..…...20 Chapter 3: Elastase treatment reliably produces AAA……...........................…………..………26-34

Introduction ………………………………………………………..........................................................………………..26

Materials and Methods………………………………………….....................................................…………….……..26-28

Results ………………………………………………………………...........................................................…….………..28-29

Conclusions ……………………………………………….........................................................………………………...29

Chapter 4: Antioxidants fail to lower hydrogen peroxide in Angiotensin II model………….35-37

Introduction ………………………………..........................................................………………………………………..35

Materials and Methods…………………………………….....................................................………………….……..35-36

Results ……………………………………………………...............................................................………………………36

Conclusions ………………………………………………............................................................……………………….36-37

Chapter 5: Discussion ……….………………...................................…………………………………..39-42

Summary and Conclusions ……...…………...............................................……………………………………….…39

Interpretations…………………………………………......................................................…………….……….……….39-41 Future Directions ……………………………......................................................……………………………………….41-42 References ………………………………….......................................………………………………………43-46

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