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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。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。本项目将使用受控的柴油机废气人体吸入暴露作为模型，以确定吸入DE暴露是否以浓度相关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 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.