Ultrafine Particle-Induced Oxidative Stress

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DESCRIPTION (provided by applicant): Exposure to ambient air particulate matter is associated with increased risk for cardiovascular disease. UItrafine particles (UFP) may be important in this regard because of their high surface area, oxidant capacity, and ability to enter the lung interstitium and vascular space. These studies will test the hypothesis that exposure to ambient UFP causes endothelial dysfunction in both the pulmonary and systemic vascular beds, via oxidant mechanisms. The investigators will determine whether people with type 2 diabetes, who have underlying vascular dysfunction related to oxidative stress, will be more susceptible than healthy subjects to the acute vascular effects of UFP exposure. These studies will consist of three human exposure protocols, using the Harvard Ultrafine Ambient Particle Concentrator. The first protocol will examine effects in healthy subjects, the second protocol will examine effects in age-matched subjects with type 2 diabetes, and the third protocol will assess the role of supplementation with antioxidant vitamins C and E in preventing the vascular effects of UFP exposure. Pulmonary vascular effects will be assessed by changes in the diffusing capacity for carbon monoxide, and the pulmonary capillary blood volume. Systemic vascular effects will be measured using forearm flow-mediated dilatation, with and without nitroglycerin. In addition, the investigators will measure the oxidant capacity of the concentrated ultrafine aerosol, and the level of systemic oxidative stress using glutathione redox balance and plasma lipid peroxides. Confirmation of the hypothesis that UFP oxidant capacity mediates vascular effects will have important implications for air pollution regulatory efforts, and will provide new approaches for the prevention of cardiovascular health effects.