Mechanism of ambient particulate matter assosicated cardiovascular diseases: a fe

环境颗粒物与心血管疾病相关的机制：a fe

• 批准号: 7909348
• 负责人: QINGSHAN QU
• 金额: $ 2.8万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-06 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7909348
• 关键词: Address; Admission activity; Age; Air; Air Pollutants; Airborne Particulate Matter; Animals; Apolipoprotein E; Area; Atherosclerosis; Behavior; Biological Assay; Biological Markers; Blood specimen; Breathing; C-reactive protein; Caliber; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Characteristics; Chemicals; China; Chinese People; Cities; Climate; Coal; Communities; Complex; Data; Data Analyses; Databases; Dust; Educational Status; Elderly; Elements; Environmental Health; Ethnic Origin; Exposure to; Functional disorder; Future; Gender; Goals; Health Hazards; Heart Rate; Hospitals; Human; Individual; Interleukin-6; Leukocytes; Life Style; Link; Measures; Monitor; Monocyte Chemoattractant Protein-1; Morbidity - disease rate; Mus; Nature; Nickel; Occupational Exposure; Outcome Study; Particle Size; Particulate Matter; Pathway interactions; Pilot Projects; Play; Population; Protein C; Quality Control; Records; Recruitment Activity; Regulation; Reporting; Research; Risk; Role; Sampling; Series; Socioeconomic Status; Source; Testing; Time; Time Series Analysis; Transition Elements; Vanadium; Variant; Vascular Cell Adhesion Molecule-1; air sampling; base; cardiovascular disorder risk; cohort; food consumption; heart rate variability; insight; mortality; mouse model; particle; pollutant; population based; programs; public health relevance; quality assurance; respiratory; socioeconomics; vascular inflammation

DESCRIPTION (provided by applicant): It has been well documented that exposure to fine ambient air particulate matter (PM2.5) induces consistent increased risk for cardiovascular disorders (CVD) in humans at the levels currently encountered in the U.S. However, the mechanism(s) and component(s) responsible for PM2.5 associated cardiovascular effects are still unknown. In our recent subchronic inhalation study, we observed that dramatic increases in heart rate and decreases in heart rate variability occurred in the ApoE-/- mouse model on days when PM2.5 contained elevated concentrations of nickel (Ni) as compared to days with typically lower Ni exposure. We further found in humans that Ni and vanadium best explained the variation of the NMMAPS PM10 mortality risk coefficients across cities. Therefore, we hypothesize that Ni is a major component responsible for PM2.5 associated CVD. It has been difficult, however, to test this hypothesis due to lack of appropriate populations with adequate combination of exposures to both PM2.5 and Ni in the U.S. Recently, we identified two large cities in China, which have exposures to similar ambient PM2.5 mass concentrations but very different levels of Ni (~500ng Ni/m3 in Jinchang and ~10 ng Ni/m3 in Zhanye). Therefore, we propose to evaluate the feasibility of using these ideal and unique populations to examine the potential roles of Ni in PM2.5 associated CVD through population- based mortality and morbidity and panel-based biomarker studies. The specific aims of the study are: 1) to examine the feasibility of conducting time-series analyses of CVD mortality and morbidity in the overall populations of the two Chinese cites to identify the potential mechanistic roles of Ni in PM2.5 associated CVD; 2) to determine whether or not the commonly used CVD biomarkers can be employed to evaluate the role of Ni in PM2.5 related CVD in the identified populations. The candidate biomarkers of CVD include proinflammatory markers [IL-6, and C reactive protein (CRP)]; markers of leukocyte recruitment [monocyte chemoattractant protein 1 (MCP-1)]; and endothelial dysfunction biomarkers (ICAM and VCAM). This study will provide insights into the role of, and mechanism for action of a highly likely PM2.5 component in terms of inducing CVD. This study should have significant implications for both research and legislative regulation in controlling the health hazards associated with ambient PM exposure. PUBLIC HEALTH RELEVANCE: Particulate matter (PM) in ambient air is a mixture and a ubiquitous pollutant that induces consistent increase in hospital admission and death of cardiovascular disorders (CVD) in humans at the levels currently encountered in the U.S. However, why PM causes CVD is still unknown. This study was proposed to address the role that nickel may play in PM associated CVD. The study is relevant to the major environmental health issues and should have significant implications for both research and legislative regulation in controlling the health hazards associated with ambient PM exposure.

描述（由申请人提供）：已经有充分的文献证明，暴露于精细的环境空气颗粒物（PM2.5）会导致人类目前在美国遇到的水平上的心血管疾病（CVD）的风险持续增加，但是，机制和组件负责PM2.5相关性心血管效应，仍然尚不清楚。在我们最近的亚少数吸入研究中，我们观察到，与通常较低NI暴露的天数相比，PM2.5含有较高的镍（NI）的天数，在PM2.5含有较高浓度的镍（NI）时，心率急剧增加和心率变异性降低发生。我们在人类中进一步发现，NI和钒最好地解释了整个城市的NMMAPS PM10死亡率风险系数的变化。因此，我们假设Ni是负责PM2.5相关CVD的主要组成部分。然而，由于缺乏适当的人群，在美国最近对PM2.5和NI的接触组合的适当组合，因此很难检验这一假设，我们在中国确定了两个大城市，这些城市在类似的环境PM2.5质量浓度中曝光，但Ni级别非常不同（〜500ng ni/m3（〜500ng ni/m3）（〜500ng ni/m3 in jinchang and 〜10 ng ni/〜10 ng ni/m3）。因此，我们建议评估使用这些理想和独特的人群通过基于人群的死亡率和发病率以及基于面板的生物标志物研究来检查Ni在PM2.5相关CVD中的潜在作用的可行性。该研究的具体目的是：1）检查两个中国引用的总体中CVD死亡率和发病率的时间序列分析的可行性，以确定Ni在PM2.5相关CVD中的潜在机械作用； 2）确定是否可以使用常用的CVD生物标志物来评估Ni在PM2.5相关的CVD中的作用。 CVD的候选生物标志物包括促炎标记[IL-6和C反应性蛋白（CRP）]；白细胞募集的标记[单核细胞趋化剂蛋白1（MCP-1）]；和内皮功能障碍生物标志物（ICAM和VCAM）。这项研究将为诱导CVD而言，对极有可能的PM2.5组件的作用的作用和作用机制提供见解。这项研究在控制与环境PM暴露相关的健康危害方面对研究和立法监管都具有重大影响。 公共卫生相关性：环境空气中的颗粒物（PM）是一种混合物和无处不在的污染物，可引起人类目前在美国遇到的水平的医院入院和心血管疾病（CVD）的持续增加和死亡，但是为什么PM会导致CVD导致CVD尚不清楚。提出了这项研究来解决镍在PM相关CVD中可能扮演的角色。该研究与主要的环境健康问题有关，在控制与环境PM暴露相关的健康危害方面，应对研究和立法监管产生重大影响。