Ultrafine Particle-Induced Oxidative Stress

描述（由申请人提供）： 暴露于环境空气颗粒物与心血管疾病风险增加有关。 超细颗粒（UFP）在这方面可能是重要的，因为它们的高表面积、氧化能力和进入肺动脉和血管空间的能力。这些研究将检验暴露于环境UFP通过氧化机制引起肺和全身血管床内皮功能障碍的假设。研究人员将确定2型糖尿病患者是否比健康受试者更容易受到UFP暴露的急性血管效应的影响。这些研究将包括三个人体暴露方案，使用哈佛超细环境颗粒浓缩器。第一个方案将检查对健康受试者的影响，第二个方案将检查年龄匹配的2型糖尿病受试者的影响，第三个方案将评估补充抗氧化剂维生素C和E在预防UFP暴露的血管效应中的作用。 将通过一氧化碳弥散量和肺毛细血管血容量的变化评估肺血管效应。 将使用前臂血流介导的扩张（含和不含硝酸甘油）测量全身血管效应。此外，研究者将测量浓缩超细气雾剂的氧化能力，以及使用谷胱甘肽氧化还原平衡和血浆脂质过氧化物的全身氧化应激水平。 UFP氧化能力介导血管效应这一假设的证实将对空气污染监管工作产生重要影响，并将为预防心血管健康效应提供新的方法。

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.