Project 1 - Cardiometabolic Injury due to VOCs

项目 1 - VOC 引起的心脏代谢损伤

• 批准号: 10693801
• 负责人: Aruni Bhatnagar
• 金额: $ 31.96万
• 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/10693801
• 关键词: Acceleration; 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; 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; particle; 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 该项目的总体目标是评估与超级基金相关的波动的影响 关于心脏代谢疾病的有机化合物（VOC），这是基本条件 导致糖尿病，心血管疾病和肝病。诸如三氯乙烯之类的VOC， 苯，丙烯醛，甲醛，二甲苯和丁二烯最多是主要关注的化学物质 超级基金网站和以前的大量工作表明，接触VOC可能会有多种多样 不利的健康影响。然而，是否接触与与 超级基金站点附近的邻里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的动物的广泛研究表明，慢性 暴露于低剂量的VOC可能会增加血压，造成血管损伤，加速加速 动脉粥样硬化，诱导肝病。但是，VOC的心脏代谢风险具有 没有评估和纵向数据以询问暴露响应关系是 丢失的。因此，为了评估VOC施加的CMD风险，我们将检验以下假设 VOCS加剧/诱导的血管和肝功能障碍，导致一系列事件 这增加了CMD风险。为了评估VOC暴露的影响，我们将检查1200名居民 杰斐逊县（Jefferson County 车道和酿酒厂农场，以及高VOC排放，例如鲁布伯敦社区。 在每个参与者中，我们将通过测量动脉刚度评估CMD风险，这是肝细胞的标志 死亡以及生物标志物的套件，指示糖尿病，心血管和肝脏的风险 疾病。确定人群级的VOC暴露及其与CMD相关的关系 医院入院和死亡率，我们将建立一个VOC监视器网络来衡量VOC 整个杰斐逊县的水平，并监视尿液中的家用废水 代谢物。我们将每隔一个月一次监视3年的废水，并评估 哪些人口水平的暴露估计反映了环境空气VOC水平和个人级别 暴露（AIM 1），以及这些估计与人口级和个体级别的CMD有关 风险。为了获得纵向数据，我们将检查CMD的进展并确定 个人级别和社区级别的VOC与血管的关联和 心脏代谢风险的肝功能和其他指数。这将有助于我们评估如何 接触和/或居民靠近超级基金站点会影响CMD的风险，这 与城市社区中背景VOC曝光相关的风险差异过多。 我们预计该项目的完成将导致定量风险模型的发展 以及对居民VOC暴露的其他CMD风险的严格估计。