Environmental Exposure and Cardiometabolic Disease

环境暴露与心血管代谢疾病

• 批准号: 10354688
• 负责人: Sanjay Srivastava
• 金额: $ 218.9万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10354688
• 关键词: Action Research; Advanced Development; Affect; Animal Experiments; Animal Model; Animals; Area; Atmosphere; Awareness; Biological; Biological Markers; COVID-19; Cardiology; Cardiometabolic Disease; Cardiovascular Diseases; Chemical Exposure; Chemicals; Chemistry; Communities; Community Outreach; Complement; Cost Measures; Critical Pathways; Data; Data Analyses; Data Storage and Retrieval; Decision Making; Development; Devices; Diabetes Mellitus; Disease Pathway; Education and Outreach; Ensure; Environment; Environmental Exposure; Environmental Science; Epidemic; Epidemiology; Etiology; Evaluation; Exposure to; Foundations; Funding; Future; Generations; Goals; Growth; Hazardous Chemicals; Hazardous Substances; Hazardous Waste Sites; Health; Heart Diseases; Hepatology; Human; Incidence; Industrialization; Injury; Investigation; Knowledge; Lead; Mass Spectrum Analysis; Measures; Membrane; Metabolism; Methods; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathway interactions; Population; Postdoctoral Fellow; Predisposition; Prevalence; Private Sector; Procedures; Process; Public Health; Public Sector; Research; Research Infrastructure; Research Personnel; Research Project Grants; Research Support; Research Training; Resources; Risk; Sampling; Science; Severities; Site; Superfund; Technology; Tissue Sample; Toxic effect; Toxicology; Training; Training Programs; Universities; Validation; Work; animal tissue; base; biobank; cardiometabolism; community engagement; computer code; data archive; data management; data sharing; detection method; education resources; experience; exposed human population; fatty liver disease; graduate student; human population study; human tissue; innovation; interest; member; new technology; novel; novel marker; obesity development; outreach program; pollutant; programs; remediation; repository; resilience; response; superfund chemical; superfund site; tool; translational medicine; volatile organic compound

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.

项目摘要（总体） 该提议将继续增长和扩展路易斯维尔大学超级基金中心建立的 2017年。目前，该中心支持有关挥发性有机化学的心脏代谢作用的研究 （VOC）与超级基金计划高度相关。中心调查人员进行行动方式 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） 在超级基金和相关地点发现的化学物质（VOC）。使用高吞吐量质谱和 创新的基于机制的生物标志物，动物实验和人口研究的套件，中心 调查有助于发现和验证暴露和暴露的新生物标志物 心脏代谢损伤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，用于开发污染物的气氛，以供动物暴露并测量独特而敏感 反映心脏代谢损伤的生物终点。此外，中心支持的工作导致 开发新方法和设备，用于量化采用高级的大气水平 技术并提供危险废物站点的精确但低成本的测量。和以前一样 该中心的目标是对VOC的心脏代谢毒性进行最先进的研究和对 确定它们如何影响裸露人群中的心脏代谢疾病（CMD）患病率和严重程度。 这些研究将通过动物的行动方式研​​究来补充，以鉴定分子 以及导致VOC毒性的细胞机制。这些研究的结果将继续做出贡献 既可以发现敏感和健壮的生物标志物的发现和验证，这些标志物可用于评估 暴露，代谢和毒性的程度。中心调查人员正在创建用于检测的新技术 在低环境水平上的VOC可以使未来的接触评估活动。高级中心成员 在环境领域教育和培训初级调查员，研究生和博士后研究员 科学，并促进相关的社区意识和参与，以增强相互双向 了解暴露风险和暴露的健康影响。中心的发现和发现 将转移到受影响的社区，公共部门和私营部门的最终用户以及其他利益相关者。为了 未来的使用和分析，所有人类和动物组织的样本以及中心期间收集的所有数据 调查将存储在计算机编码的生物库中。总体而言，中心的扩张和增长 活动将提高其贡献并导致严格的评估，并更好地理解 这些关于肥胖，糖尿病和心血管疾病的危险化学物质。