EFFECT OF DIESEL EXHAUST PARTICULATE EXPOSURES: THE ROLE OF OXIDATIVE STRESS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. With this overall study, we propose to explore whether human exposure to diesel exhaust (DE) results in alteration of endothelial homeostasis and evidence of oxidative stress. Ambient fine particulate matter exerts cardiovascular health effects via alteration of endothelial homeostasis, through a mechanism mediated by oxidative stress. This project will use a controlled human inhalation exposure to diesel exhaust as a model to determine whether exposure to inhaled DE is associated with endothelial dysfunction in a concentration-related manner. Outcomes include symptoms, spirometry, flow-mediated dilation of the brachial artery, exhaled nitric oxide, and blood measures of inflammation, thrombosis, endothelial function and oxidative stress. These controlled exposure crossover experiments, in which healthy or metabolic syndrome subjects are exposed to diluted DE or filtered air, and then are evaluated to determine exposure-effect relations. Pilot studies have determined that experimental procedures can be conducted as planned, that the exposures are tolerable, that the occurrence of symptoms can be documented, and have established the success of exposure blinding efforts. These pilot studies validated dose-response relationships between DE and sub-clinical vascular effects. They have also informed us of data that determined choices of exposure doses, outcomes, and sample size calculations.