Date of Award

Spring 2024

Degree Type

Thesis

Department

Biological Sciences

Director of Thesis

Dr. A. Phillip Owens III, Ph.D.

First Reader

Dr. Andy Schumpert, Ph.D.

Second Reader

Dr. Andy Schumpert, Ph.D.

Abstract

Cardiovascular diseases (CVDs) remain the leading cause of mortality in the world despite extensive research. As a type of CVD, abdominal aortic aneurysm (AAA) represents a critical medical condition characterized by the localized dilation of the abdominal aorta. Complications from aneurysm development results in catastrophic aortic rupture, which leads to mortality more than 80% of the time. As aneurysm development is typically asymptomatic, many AAAs remain untreated until they present a serious risk of rupture. Additionally, no pharmaceutical treatment exists for AAAs, with the only option being surgical intervention. Despite advancements in diagnostic methods and surgical techniques, the pathogenesis of AAAs remains understudied. Increased emphasis has been placed on the role of inflammation and cellular signaling in response to vascular injury, with vascular smooth muscle cell (VSMC) dysfunction and extracellular matrix remodeling contributing to aneurysm progression. Elucidating the role of inflammatory proteases and protease-activated receptors (PARs) like PAR2 in conditions like AAA is essential to improving our understanding of this disease and its progression. Our current study examined the effect of global Par2 deficiency in an elastase model of murine AAA. Par2 deficiency resulted in decreased aneurysm diameter and higher survival rates when compared to Par2 proficient mice. Additionally, PAR2 -/- mice had decreased infiltration of macrophages and increased levels of type I collagen in the vessel walls, indicating less inflammation and improved stability and structural health of the aorta versus proficient controls. However, the incidence of rupture was not affected by PAR2 deficiency suggesting aneurysm stability could be influenced by more than PAR2 signaling. In conclusion, our study offers insights into the role of PAR2 in aneurysm development and progression, which may warrant therapeutic intervention.

First Page

1

Last Page

41

Rights

© 2024, John Joseph Pitstick, A. Phillip Owens III Ph.D.

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