Ultrafine Particle-Induced Oxidative Stress

描述(由申请人提供)： 暴露在环境空气颗粒物中会增加患心血管疾病的风险。超细颗粒(UFP)在这方面可能很重要，因为它们具有较高的表面积、氧化能力以及进入肺间质和血管空间的能力。这些研究将检验这一假设，即暴露在环境中的UFP通过氧化机制导致肺和全身血管床的内皮功能障碍。研究人员将确定，患有与氧化应激相关的潜在血管功能障碍的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，使用哈佛大学的超细环境颗粒物集中器。第一个方案将检查健康受试者的效果，第二个方案将检查年龄匹配的2型糖尿病患者的效果，第三个方案将评估补充抗氧化剂维生素C和E在预防UFP暴露的血管影响方面的作用。肺血管效应将通过一氧化碳扩散能力和肺毛细血管血容量的变化来评估。使用和不使用硝酸甘油的前臂血流介导的扩张术将测量全身血管效应。此外，研究人员还将使用谷胱甘肽氧化还原天平和血浆过氧化脂质来测量浓缩超细气溶胶的氧化能力，以及全身氧化应激的水平。证实UFP氧化剂能力介导血管效应的假设将对空气污染监管工作具有重要意义，并将为预防心血管健康影响提供新的方法。

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.