Date Available

5-6-2014

Year of Publication

2014

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Medicine

Department/School/Program

Nutritional Sciences

First Advisor

Dr. Bernhard Hennig

Abstract

Cardiovascular disease remains the leading cause of death in Western societies. Endothelial dysfunction is one of the initiating steps in the development of atherosclerosis. While there is a strong correlation with a person’s genetics, lifestyle factors including smoking, physical activity, and diet can significantly increase a person’s susceptibility to the development of atherosclerosis. In addition to these lifestyle factors, there is a strong body of evidence linking exposure to environmental pollutants including persistent organic pollutants such as polychlorinated biphenyls to increased cardiovascular disease and mortality. It has been well-established that exercise protects against cardiovascular disease, but whether exercise can modulate PCB-induced cardiovascular inflammation and dysfunction is unknown.

To investigate the effects of exercise on PCB-induced cardiovascular disease, two murine models of atherosclerosis, the ApoE-/- and the LDLr-/- mouse were utilized. Risk factors for cardiovascular disease including adiposity, glucose intolerance, hyperlipidemia, hypertension, oxidative stress, and inflammation, were assessed in these two models as well as mean atherosclerotic lesion size. Exercise positively modulates several risk factors associated with cardiovascular disease including hypertension, hyperlipidemia, adiposity and obesity, systemic levels of oxidative stress, inflammation, and glucose tolerance. Exercise significantly reduced mean lesion size in vehicle-treated animals. To assess the mechanism of protection of exercise in chapter 4, vascular reactivity studies were performed to measure endothelial function after exposure to PCB 77. Exercise prevented PCB-impaired endothelial function implicating the role of superoxide as a cause of impairment. Exercise upregulated phase II antioxidant enzymes. The work in this dissertation demonstrates several protective properties of exercise against PCB-induced cardiovascular disease; however, additional studies are needed to determine if exercise enhances metabolism and excretion of these environmental pollutants.

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