Project 1 - Cardiometabolic Injury due to VOCs

项目 1 - VOC 引起的心脏代谢损伤

• 批准号: 10354689
• 负责人: Aruni Bhatnagar
• 金额: $ 32.71万
• 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/10354689
• 关键词: Acrolein; Affect; Air; Animals; Area; Atherosclerosis; Benzene; Bile Acids; Biological Markers; Blood Platelets; Blood Pressure; Blood Vessels; Butadiene; Carcinogens; Cardiometabolic Disease; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chemicals; Chronic; Collaborations; Communities; County; Data; Data Analyses; Development; Diabetes Mellitus; Disease Progression; Dose; Environmental Exposure; Enzymes; Event; Exposure to; Farm; Formaldehyde; Functional disorder; Goals; Hazardous Chemicals; Health; Hepatic; Hepatocyte; Hepatotoxicity; Hospital Mortality; Hospitalization; Human; Individual; Injury; Insulin Resistance; Kentucky; Keratin; Lipids; Liquid substance; Liver; Liver diseases; Location; Measurement; Measures; Metabolic Diseases; Metabolism; MicroRNAs; Modeling; Monitor; Neighborhoods; Participant; Plasma; Population; Process; Risk; Serology; Serum; Steatohepatitis; Superfund; Target Populations; Testing; Time; Toluene; Trichloroethylene; Variant; Vascular Diseases; Water; Work; Xylene; arterial stiffness; blood glucose regulation; blood pressure elevation; carcinogenicity; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; circulating biomarkers; cohort; data management; diabetes risk; disorder risk; exposed human population; fatty liver disease; indexing; land use; landfill; liver biopsy; monocyte; mortality; primary endpoint; response; stem cells; superfund site; toxicant; urinary; vascular injury; volatile organic compound; wastewater monitoring

PROJECT SUMMARY The overall goal of this project is to assess the impact of exposure to Superfund-relevant volatile organic compounds (VOCs) on cardiometabolic disease, the underlying conditions that contributes to diabetes, cardiovascular and liver diseases. VOCs such as trichloroethylene, benzene, acrolein, formaldehyde, xylene and butadiene are major chemicals of concern at most Superfund sites and extensive previous work suggests the exposure to VOC could have a variety of adverse health effects. Nevertheless, whether exposure to VOCs at levels relevant to neighborhood adjacent to Superfund sites could adversely affect cardiometabolic health remains unknown. Our extensive studies with animal exposed to different VOCs suggest that chronic exposure to low dose VOCs could increase blood pressure, inflict vascular injury, accelerate atherosclerosis, and induce liver disease. Nevertheless, the cardiometabolic risk of VOCs has not been evaluated and longitudinal data to interrogate exposure-response relationships are missing. Hence, to assess CMD risk imposed by VOCs, we will test the hypothesis that exposure to VOCs exacerbates/induces vascular and hepatic dysfunction leading to a cascade of events that increase CMD risk. To assess the impact of VOC exposures, we will examine 1200 residents of Jefferson County, including those who live in areas adjacent to Superfund sites such as Lee’s Lane and Distiller Farm, as well as high VOC emission, such as the Rubbertown neighborhood. In each participant, we will assess CMD risk by measuring arterial stiffness, marker of hepatocyte death, as well as suite of biomarkers indicative of risk for diabetes, cardiovascular and liver diseases. To determine population-level VOC exposure and its relationship with CMD-related hospital admissions and mortality, we will establish a network of VOC monitors to measure VOC levels throughout Jefferson County and monitor domestic wastewater for urinary VOC metabolites. We will monitor wastewater every other month for 3 years, and assess the extent to which population-level exposure estimates reflect ambient air VOC levels and individual-level exposure (Aim 1), and how these estimates relate to population-level and individual-level CMD risk. To obtain longitudinal data, we will examine CMD progression and determine the association between individual-level and community-level VOC exposures with vascular and hepatic function and other indices of cardiometabolic risk. This will help us in assessing how VOC exposure and/or residential proximity to Superfund sites affects the risk of CMD and this excessive risk differs from that imposed by background VOC exposures in urban neighborhood. We expect that completion of this project will lead to the development of quantitative risk models and rigorous estimates of the additional CMD risk attributable to residential VOC exposures.

项目摘要 本项目的总体目标是评估与超级基金相关的波动性风险敞口的影响。 有机化合物（VOCs）对心脏代谢疾病的影响， 导致糖尿病、心血管疾病和肝脏疾病。挥发性有机化合物如三氯乙烯， 苯、丙烯醛、甲醛、二甲苯和丁二烯是最受关注的主要化学品 超级基金网站和以前的大量工作表明，暴露于VOC可能有各种各样的 对健康的不良影响。尽管如此，接触挥发性有机化合物的水平是否与 邻近超级基金站点的社区可能会对心脏代谢健康产生不利影响 未知我们对暴露于不同VOC的动物进行的广泛研究表明， 暴露于低剂量的VOCs可增加血压，造成血管损伤，加速 动脉粥样硬化，并诱发肝脏疾病。然而，VOC的心脏代谢风险 未进行评价，询问疗效-反应关系的纵向数据 失踪了因此，为了评估VOC造成的CMD风险，我们将检验暴露 挥发性有机化合物加剧/诱导血管和肝功能障碍，导致一系列事件 这增加了CMD风险。为评估挥发性有机化合物的影响，我们会对1200名居民进行调查， 杰斐逊县，包括那些谁住在邻近地区的超级基金网站，如李的 巷和蒸馏农场，以及高挥发性有机化合物排放，如橡胶镇附近。 在每个参与者中，我们将通过测量肝细胞标志物动脉硬度来评估CMD风险。 死亡，以及一套指示糖尿病、心血管和肝脏风险的生物标志物 疾病确定人群水平的VOC暴露及其与CMD相关的关系 我们会设立挥发性有机化合物监察网络， 水平在整个杰斐逊县和监测家庭废水的尿挥发性有机化合物 代谢物。我们将每隔一个月监测一次废水，持续3年，并评估废水的程度， 人口水平暴露估计反映环境空气VOC水平和个人水平 暴露量（目标1），以及这些估计与人群水平和个人水平CMD的关系 风险为了获得纵向数据，我们将检查CMD进展并确定 个人水平和社区水平的VOC暴露与血管和 肝功能和其他心脏代谢风险指标。这将有助于我们评估VOC如何 接触和/或住宅接近超级基金网站影响CMD的风险，这 过量风险不同于城市社区背景VOC暴露所造成的风险。 我们预计，该项目的完成将导致定量风险模型的开发 以及对住宅挥发性有机化合物暴露引起的额外CMD风险的严格估计。