Date of Graduation

2017

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Physiology, Pharmacology & Neuroscience

Committee Chair

Paul D Chantler

Committee Co-Chair

Stephen E Alway

Committee Member

Jefferson C Frisbee

Committee Member

Ivan M Olfert

Committee Member

Emidio E Pistilli

Committee Member

David P Siderovski

Abstract

Aortic compliance is important for dampening pulsatile flow and delivery of continuous flow to the periphery. Aortic compliance is regulated by extracellular matrix composition and endothelial derived nitric oxide. Disruption of aortic endothelium or extracellular matrix can lead to the development of aortic stiffness an independent risk factor of cardiac events and mortality. Over the past decade perivascular adipose tissue (PVAT) surrounding the vasculature has come to light as an important regulator of artery function. The main focus of this dissertation is to evaluate the role PVAT surrounding the aorta in mediating endothelial relaxation in health and disease. Specifically, metabolic syndrome (MetS) and chronic stress induced depressive states.;The United States has a high prevalence of both MetS and depressive states, 34% and 17% respectively. Additionally, the co-prevalence of depressive states with MetS is common. Both MetS and depressive states are associated with vascular dysfunction, in part, mediated through an increase of pro-inflammatory cytokines and oxidative stress. Little is known about the impact of MetS on PVAT regulation of the aorta and the impact of depressive states or depressive states concomitant with MetS on PVAT is unexplored.;Aerobic exercise training is recognized to have antioxidant and anti-inflammatory properties and promotes vascular health. Exercise training has been shown to reduce aortic stiffness and reduce the risk of cardiac events and mortality. Likewise exercise treatment of MetS or depressive state yields beneficial effects and limits the vascular pathology of these disease state. However, the actions of exercise on PVAT in health and disease are poorly understood. In order to evaluate these gaps in knowledge, I purpose the following specific aims for this dissertation: 1. Determine Metabolic Syndrome's impact on Thoracic Aorta PVAT and PVAT derived TNFalpha contribution to aortic dysfunction 2. Determine if UCMS impacts the regulation of PVAT on aortic function 3. Test the therapeutic effectiveness of aerobic exercise on PVAT and its regulation of aortic function.;The results of this study will establish the role of PVAT in mediating aortic dysfunction associated with MetS and depressive state. Additionally, this work will identify key disease specific mediators of PVAT regulation of aortic function. Finally, this work will establish mechanisms through which exercise mediates beneficial aortic function.

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