Environmental Exposure and Cardiometabolic Disease

项目概要（总体） 该建议是在路易斯维尔大学建立一个超级基金中心。该中心将支持研究 关于与超级基金高度相关的挥发性有机化学品（VOCs）对心脏代谢的影响 程序.中心研究人员将进行作用模式研究，以揭示毒性的关键途径， 确定超级基金中发现的化学品（VOC）的毒理学终点（心脏代谢变化）， 相关网站。使用高通量代谢组学和质谱方法，动物实验和 人类群体研究，中心的研究将有助于发现和验证新的生物标志物， 这将为今后的补救战略奠定基础。这些 研究将采用最先进的工具来开发动物暴露的污染物大气，并测量 反映心脏代谢损伤的独特且敏感的生物学终点。此外， 该中心将导致开发新的方法和设备，用于量化大气中的VOC水平， 将采用先进的技术，并提供精确的，但低成本的测量危险废物的网站。的 该中心的主要目标是对挥发性有机化合物的心脏代谢毒性进行最先进的研究 并确定他们如何影响心脏代谢病（CMD）的患病率和严重程度， 人口。这些研究将通过动物中的作用机制研究进行补充，以确定 导致VOC毒性的分子和细胞机制。中心研究人员还将确定 特定条件，如营养状况和肥胖，以及对VOC毒性和试验敏感性增加 治疗干预可以减轻VOC暴露对心脏代谢的急性和慢性影响。的 这些研究的结果将有助于发现和验证敏感和可靠的生物标志物 可用于评估接触、代谢和毒性的程度。研究人员将创建 在低环境水平下检测VOC的新技术，以便将来进行暴露评估 活动高级中心成员将教育和培训初级研究人员，研究生和博士后 环境科学领域的研究员，并促进相关社区的认识和参与， 加强对接触风险和接触对健康影响的双向了解。这些发现 该中心的发现将被转移到受影响的社区，公共和私营部门的最终用户， 和其他利益相关者。为了将来的使用和分析，所有人类和动物组织样本以及所有数据 中心研究期间采集的样本将储存在计算机编码的生物储存库中。集体，中心 这些活动将导致对这些危险化学品的影响进行严格的评估和更好的了解 肥胖症、糖尿病和心血管疾病。

PROJECT SUMMARY (Overall) This proposal is to establish a Superfund Center at the University of Louisville. This Center will support research on the cardiometabolic effects of volatile organic chemicals (VOCs) that are of high relevance to the Superfund Program. Center investigators will 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 metabolomic and mass spectrometry approaches, animal experiments and human population studies, Center investigations will aid in the discovery and validation of novel biomarkers of both exposure and cardiometabolic injury that would lay the foundation for future remediation strategies. These studies will 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 will lead to the development of new methods and devices for quantifying atmospheric levels of VOCs that will employ advanced technologies and offer precise, but low-cost measurements of hazardous waste sites. 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. Center investigators will also identify specific conditions such as nutritional status and obesity and increase susceptibility to VOC toxicity and test therapeutic interventions that can attenuate acute and chronic cardiometabolic effects of VOC exposures. The findings of these studies will 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 will create new technologies for detecting VOCs at low environmental levels to enable future exposure assessment activities. Senior Center members will 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, Center activities will lead to rigorous evaluation and better understanding of the effects of these hazardous chemicals on obesity, diabetes and cardiovascular disease.