Environmental Exposure and Cardiometabolic Disease

项目概要（总体） 这项建议是继续发展和扩大路易斯维尔大学超级基金中心成立于 2017.目前，该中心支持挥发性有机化学品对心脏代谢影响的研究 （VOC）与超级基金计划高度相关。研究中心研究者开展行动模式 研究以阐明毒性的关键途径并确定毒理学终点（心脏代谢变化） 在超级基金和相关场所发现的化学品（VOC）。使用高通量质谱和 基于机制的生物标志物、动物实验和人群研究的创新套件，中心 研究有助于发现和验证暴露和 这将为未来的补救策略奠定基础。这些研究采用 最先进的工具，用于开发动物暴露的污染物大气，并测量独特和敏感的 反映心脏代谢损伤的生物学终点。此外，该中心支持的工作正在导致 开发新的方法和设备，用于量化大气中的VOC水平， 技术，并提供精确的，但低成本的测量危险废物场地。和以前一样，少校 该中心的目标是对VOCs的心脏代谢毒性进行最先进的研究， 确定它们如何影响暴露人群中心脏代谢病（CMD）的患病率和严重程度。 这些研究将通过动物中的作用机制研究来补充，以确定分子 以及导致VOC毒性的细胞机制。这些研究的结果将继续有助于 发现和验证敏感和强大的生物标志物，可用于评估 接触程度、代谢和毒性。中心的研究人员正在创造新的技术， 低环境水平的挥发性有机化合物，以使未来的接触评估活动。高级中心成员 教育和培训环境领域的初级调查员、研究生和博士后研究员 科学，并促进相关社区的认识和参与，以加强相互双向 了解暴露风险和暴露对健康的影响。该中心的发现和发现 将转移到受影响社区、公共和私营部门的最终用户以及其他利益攸关方。为 未来的使用和分析，所有人类和动物组织样本以及中心期间收集的所有数据 调查结果将储存在计算机编码的生物储存库中。总的来说，中心的扩大和发展 这些活动将加强其贡献，并导致严格评价和更好地了解 这些有害化学物质对肥胖、糖尿病和心血管疾病的影响。

PROJECT SUMMARY (Overall) This proposal is to continue to grow and expand the University of Louisville Superfund Center established in 2017. Currently, the Center supports research on the cardiometabolic effects of volatile organic chemicals (VOCs) that are of high relevance to the Superfund Program. Center investigators conduct mode-of-action research to unravel critical pathways of toxicity and to identify toxicological end-points (cardiometabolic changes) of chemicals (VOCs) found at Superfund and related sites. Using high throughput mass spectrometry and an innovative suite of mechanism-based biomarkers, animal experiments and human population studies, Center investigations have contributed to the discovery and validation of novel biomarkers of both exposure and cardiometabolic injury that would lay the foundation for future remediation strategies. These studies employ state-of-the-art tools to develop pollutant atmospheres for animal exposure and to measure unique and sensitive biological endpoints reflective of cardiometabolic injury. In addition, work supported by the Center is leading to the development of new methods and devices for quantifying atmospheric levels of VOCs that employ advanced technologies and offer precise, but low-cost measurements of hazardous waste sites. As before, the major objectives of the Center are to conduct state-of-the-art research on the cardiometabolic toxicity of VOCs and to determine how they affect cardiometabolic disease (CMD) prevalence and severity in exposed populations. These studies will be complemented by mode-of-action mechanistic studies in animals to identify the molecular and cellular mechanisms that contribute to VOC toxicity. The findings of these studies will continue to contribute to both the discovery and the validation of sensitive and robust biomarkers that could be used to assess the extent of exposure, metabolism and toxicity. Center investigators are creating new technologies for detecting VOCs at low environmental levels to enable future exposure assessment activities. Senior Center members educate and train junior investigators, graduate students and post-doctoral Fellows in the field of environmental science, and promote relevant community awareness and participation to enhance mutual bidirectional understanding of exposure risk and the health effects of exposure. The findings and discoveries of the Center will be transferred to affected communities, end users in public and private sectors, and other stakeholders. For future use and analysis, all samples of human and animal tissues and all data collected during Center investigations will be stored in a computer-coded biorepository. Collectively, expansion and growth of the Center activities will enhance its contribution and lead to rigorous evaluation and better understanding of the effects of these hazardous chemicals on obesity, diabetes and cardiovascular disease.