Environmental Exposure and Cardiometabolic Disease

环境暴露与心血管代谢疾病

• 批准号: 9904675
• 负责人: Sanjay Srivastava
• 金额: $ 137.89万
• 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 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904675
• 关键词: Action Research; Acute; Advanced Development; Affect; Animal Experiments; Animal Model; Animals; Area; Atmosphere; Attenuated; Awareness; Biological; Biological Markers; Cardiovascular Diseases; Cause of Death; Chemical Exposure; Chemicals; Chemistry; Chronic; Communities; Community Outreach; Complement; Cost Measures; Critical Pathways; Data; Decision Making; Detection; Development; Devices; Diabetes Mellitus; Disease; Disease Pathway; Ecology; Education and Outreach; Ensure; Environment; Environmental Exposure; Epidemic; Epidemiology; Etiology; Evaluation; Exposure to; Fatty Liver; Foundations; Future; Goals; Hazardous Chemicals; Hazardous Substances; Hazardous Waste Sites; Health; Heart Diseases; Human; Incidence; Industrialization; Injury; Investigation; Knowledge; Liver diseases; Mass Spectrum Analysis; Measures; Medical; Metabolism; Methods; Molecular; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Nutritional; Nutritional status; Obesity; Pathway interactions; Population; Postdoctoral Fellow; Predisposition; Prevalence; Private Sector; Public Health; Public Sector; Research; Research Infrastructure; Research Personnel; Research Project Grants; Research Support; Research Training; Resources; Risk; Sampling; Science; Severities; Site; Superfund; Techniques; Technology; Testing; Therapeutic Intervention; Time; Tissue Sample; Toxic effect; Toxicity Tests; Toxicology; Training; Training Programs; Translational Research; Universities; Validation; Work; animal tissue; base; biobank; cardiometabolism; computer code; data archive; data management; data sharing; education resources; experience; exposed human population; graduate student; human population study; human tissue; innovation; interest; member; metabolomics; multidisciplinary; new technology; 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 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.

项目概要（总体） 该提案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 与超级基金高度相关的挥发性有机化学物质 (VOC) 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，以揭示毒性和毒性的关键途径。 确定超级基金发现的化学品 (VOC) 的毒理学终点（心脏代谢变化）和 相关网站。使用高通量代谢组学和质谱方法、动物实验和 人口研究，中心调查将有助于发现和验证新的生物标志物 暴露和心脏代谢损伤都将为未来的补救策略奠定基础。这些 研究将采用最先进的工具来开发动物暴露的污染物气氛并测量 反映心脏代谢损伤的独特且敏感的生物学终点。此外，工作得到了 该中心将领导开发量化大气中挥发性有机化合物水平的新方法和设备， 将采用先进技术，对危险废物场提供精确但低成本的测量。这 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 并确定它们如何影响接触者中心脏代谢疾病（CMD）的患病率和严重程度 人口。这些研究将得到动物作用机制研究的补充，以确定 导致 VOC 毒性的分子和细胞机制。中心调查人员还将确定 特定条件，如营养状况和肥胖，以及增加对 VOC 毒性和测试的敏感性 可以减轻 VOC 暴露的急性和慢性心脏代谢影响的治疗干预措施。这 这些研究的结果将有助于敏感和稳健的生物标志物的发现和验证 可用于评估暴露程度、代谢和毒性。中心调查人员将创建 用于检测低环境水平挥发性有机化合物的新技术，以实现未来的暴露评估 活动。高级中心成员将教育和培训初级研究员、研究生和博士后 环境科学领域的研究员，并促进相关社区的意识和参与 加强对暴露风险和暴露对健康影响的相互了解。研究结果 该中心的发现将转移给受影响的社区、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，人类和动物组织的所有样本以及所有数据 中心调查期间收集的数据将存储在计算机编码的生物储存库中。集体地，中心 活动将导致严格评估和更好地了解这些危险化学品的影响 关于肥胖、糖尿病和心血管疾病。