All ETDs from UAB

Advisory Committee Chair

Scott W Ballinger

Advisory Committee Members

Victor M Darley-Usmar

Dale A Dickinson

Edward M Postlethwait

C Roger White

Document Type

Dissertation

Date of Award

2010

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Exposure to air pollutants are known to induce airway inflammation, decrease lung function, and worsen existing pulmonary conditions such as asthma. Additionally, air pollutant exposure has also been shown to impact cardiovascular health. Although these pollutant-induced cardiovascular effects were considered to be mediated by the direct action of pollutants upon the cardiovascular tissue and/or the indirect release of pro-inflammatory factors into the circulation, the relative contribution of the two pathways remained equivocal. Recently, several epidemiology studies associated ozone exposure with cardiovascular mortalities. However, relatively few studies to date have examined ozone in this context. In order to address our hypothesis that ozone exposure can indeed influence cardiovascular function, we modeled acute and chronic ozone exposure in C57Bl/6J and apoE-/- mice, respectively. Acutely, animals exposed to 5 days of ozone displayed increased heart rate and diastolic blood pressure. Also, their aortas exhibited impaired endothelium-dependent vascular relaxation and increased mitochondrial oxidative stress; both mechanisms are known to be involved in atherosclerosis development. In the chronic exposure models, aortas from animals exposed to 40 ozone days exhibited increased atherosclerosis lesion area, while those from animals exposed for 10 or 20 days did not. Interestingly, newborn mice exposed to 15 ozone days exhibited increased lesion area when their aortas were assessed in adulthood, suggesting that ozone exposure during childhood increases one's atherogenic risk. Finally, aortas from animals exposed to 20 ozone days exhibited increased mitochondrial oxidative stress, although it was attenuated versus animals in the acute exposure model. Since these animals did not exhibit a significant increase in atherogenesis, further studies are needed to determine whether these mitochondrial oxidative stress alterations are indicative of either a pre-atherogenic or an atheroprotective phenotype. Taken together, these findings demonstrate that both acute and chronic ozone exposures can alter functional and oxidative stress endpoints in the aorta, with age and exposure regimen acting to influence one's susceptibility. Importantly, because ozone's reactivity precludes it from entering the circulation, these findings imply that other inducers of pulmonary inflammation, such as asthma, may also affect cardiovascular health through a common pathway or mediator.

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