Preclinical Indicators & Biomarkers of Cardiovascular Effects of Arsenic Exposure

临床前指标

• 批准号: 9208858
• 负责人: Shohreh F Farzan
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9208858
• 关键词: 5 year old; Address; Adult; Advisory Committees; Affect; Archives; Arsenic; Bangladesh; Bangladeshi; Biological Markers; Biometry; Birth; Blood; Blood Pressure; Carcinogens; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Case-Control Studies; Chickens; Child; Chronic; Clinical; Cohort Studies; Data; Detection; Development; Diet; Disease; Disease Outcome; Dose; Educational workshop; Enrollment; Environmental Exposure; Environmental Pollution; Epidemiology; Exposure to; Food; Fruit; Functional disorder; Gelatinase B; Genetic Polymorphism; Genetic Predisposition to Disease; Goals; Health; Hereditary Disease; Human; Hypertension; Incidence; Individual; Inflammation; Interleukin-6; Investigation; Juice; Knowledge; Life; Life Cycle Stages; Longevity; Longitudinal Studies; Measurement; Measures; Mentors; Methodology; Molecular Epidemiology; Morbidity - disease rate; Mutation; Myocardial Ischemia; New Hampshire; Outcome; Oxidative Stress; Peripheral Vascular Diseases; Phase; Plasma; Plasminogen Activator Inhibitor 1; Play; Policy Maker; Population; Positioning Attribute; Predisposition; Pregnancy; Recruitment Activity; Research; Research Design; Research Personnel; Research Project Grants; Resources; Rice; Risk; Role; Sampling; Source; Staging; Susceptibility Gene; System; Systemic blood pressure; TNF gene; Testing; Time; Toxic Environmental Substances; Training; Urine; Water; cardiovascular disorder risk; cardiovascular health; cohort; contaminated drinking water; defined contribution; design; disorder risk; early childhood; endothelial dysfunction; experience; follow-up; hypertensive heart disease; improved; in utero; inflammatory marker; insight; mortality; population based; pre-clinical; prevent; prospective; public health relevance; response; response biomarker; screening; study population; tool; urinary

DESCRIPTION (provided by applicant) Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and evidence has suggested that exposure to environmental toxicants can increase CVD risk. Recently, high levels of arsenic (As), a leading environmental contaminant of concern have been associated with increases in CVD incidence, mortality, blood pressure, and systemic inflammation. Arsenic's effects at lower exposure levels are uncertain and studies are limited, but exposure at these low levels may be more widespread than previously thought, as data suggest that both water and dietary sources may contribute to overall As exposure in adults and children. In this study, the candidate proposes to take a lifecourse approach to examining the effects of a wider range of As exposure levels on CVD risk in both adults and children and identify preclinical indicators and biomarkers of susceptibility for CVD. In the K99 mentored phase, using existing data from two adult populations ranging in levels of As exposure, the candidate will explore the relationship between As exposure and biomarkers of CVD risk, while gaining expertise in molecular epidemiology. The candidate will test archived blood and urine samples from a U.S. population to examine the relationship between low level As exposure and markers of systemic inflammation, oxidative stress and endothelial function, which have been related to high levels of As exposure among adults. In a more highly exposed Bangladeshi population, the candidate will analyze a set of potential genetic susceptibility loci in relation t As exposure and their impact on blood pressure measurements over time. She will also advance her knowledge of molecular and cardiovascular disease epidemiology through formal coursework, workshops and guidance from a diverse advisory committee of respected researchers. In the R00 independent phase, she will apply her findings to initiate a new line of investigation testing whether in utero and/or early life As exposure influences early indicators of CVD risk in two populations of children, as pregnancy and early childhood are particularly vulnerable periods when environmental insults may impact development and thus later risk of disease. In conjunction with the Health Effects of Arsenic Longitudinal Study in Bangladesh and the New Hampshire Birth Cohort Study, the candidate will implement two parallel investigations of early indicators of CVD risk among five-year-old children exposed to As. She will test whether non-invasive measures of endothelial function are associated with varying levels of in utero and/or early childhood As exposure in these two populations, as subclinical effects of As on CVD risk may occur far in advance of clinical presentation. Developing insight into the mechanisms underlying As-related CVD and identifying biomarkers of CVD risk across life stages as they relate to As exposure, will help to define the contribution of environmental As exposure to different phases of disease, from initiation to clinical presentation. With this proposed study, the candidate is positioned to take advantage of existing resources to in order to develop independent, yet complementary projects, designed to help to fill critical gaps in our understanding of the lifelong cardiovascular health impacts of a range of As exposures levels.

描述（由申请人提供） 心血管疾病（CVD）是全球发病率和死亡率的主要原因，证据表明，暴露于环境有毒物质可以增加CVD风险。最近，高水平的砷（AS）是关注的主要环境污染物与CVD发病率，死亡率，血压和全身性炎症的增加有关。砷在较低的暴露水平下的影响尚不确定，研究受到限制，但是在这些低水平的暴露可能比以前认为的更为普遍，因为数据表明水和饮食来源都可能导致成人和儿童的暴露量总体上有助于总体上。 在这项研究中，候选人建议采取生命力方法，以检查成人和儿童的更广泛的AS暴露水平对CVD风险的影响，并确定CVD易感性的临床前指标和生物标志物。在K99的指导阶段，使用来自AS暴露水平的两个成年人群的现有数据，候选人将探索AS暴露与CVD风险的生物标志物之间的关系，同时在分子流行病学方面获得专业知识。候选人将测试来自美国人群的存档血液和尿液样本，以检查低水平与全身性炎症，氧化应激和内皮功能的标志之间的关系，这与成年人之间的AS暴露水平高有关。在更高度暴露的孟加拉国人口中，候选人将分析一组潜在的遗传易感性基因座，因为暴露及其对血压测量的影响随着时间的流逝。 她还将通过正式的课程，讲习班和尊敬的研究人员的咨询委员会的正式课程，讲习班和指导来提高自己对分子和心血管疾病流行病学的了解。在R00独立阶段，她将应用自己的发现来启动新的调查测试，无论是在子宫和/或早期生活中是否会影响曝光会影响早期指标的早期指标 当环境侮辱可能影响发育，从而随后的疾病风险时，两个儿童和幼儿时期的CVD风险特别脆弱。结合孟加拉国砷纵向研究和新罕布什尔州出生队列研究的健康影响，候选人将对暴露于AS的五岁儿童进行两次平行研究。她将测试内皮功能的非侵入性测量是否与这两个人群的暴露水平不同，因为AS对CVD风险的亚临床效应可能在临床表现之前发生较远。对与AS相关的CVD的基础机制进行洞察力，并确定与暴露相关的生命阶段中CVD风险的生物标志物，将有助于将环境的贡献定义为从临床表现到临床表现的疾病的不同阶段的贡献。通过这项拟议的研究，候选人有权利用现有资源来开发独立但互补的项目，旨在帮助填补我们对一系列AS暴露水平的终生心血管健康影响的关键空白。