THE ROLE OF OXIDATIVE STRESS IN DIESEL

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 通过这项全面的研究，我们建议探讨人类暴露于柴油机废气（DE）是否会导致内皮细胞稳态的改变和氧化应激的证据。环境细颗粒物通过氧化应激介导的机制，通过改变内皮细胞稳态，对心血管健康产生影响。 该项目使用受控的人吸入暴露于柴油机尾气作为模型，以确定暴露交通相关的空气污染是否与浓度相关的方式与内皮功能障碍相关。结果包括症状、肺量测定、肱动脉血流介导的扩张、呼出的一氧化氮、以及炎症、血栓形成、内皮功能和氧化应激的血液测量。 这些受控暴露交叉实验中，健康或代谢综合征受试者暴露于稀释的DE或过滤空气，然后进行评价以确定安全性-效应关系。初步研究已经确定，实验程序可以按计划进行，暴露是可耐受的，症状的发生可以记录，并且已经确定了暴露设盲工作的成功。这些初步研究验证了DE和亚临床血管效应之间的剂量-反应关系。他们还向我们提供了决定暴露剂量选择、结果和样本量计算的数据。

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 uses a controlled human inhalation exposure to diesel exhaust as a model to determine whether exposure traffic-related air pollution 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.