Micro-RNA Profiling and Cardiovascular Effects of Traffic Particle Exposure

Micro-RNA 分析和交通颗粒暴露对心血管的影响

• 批准号: 8336842
• 负责人: Andrea Baccarelli
• 金额: $ 15.83万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-21 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8336842
• 关键词: Accounting; Activated Partial Thromboplastin Time measurement; Air; Air Pollution; American Heart Association; Ancillary Study; Biological; Biological Markers; Blood Clot; Blood Pressure; Blood coagulation; Blood specimen; Breathing; Caliber; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cessation of life; China; Cities; Collection; DNA Methylation; Data; Data Analyses; Development; Disease Pathway; Electrocardiogram; Exposure to; Funding; Future; Gene Expression; Gene Expression Alteration; Gene Expression Profiling; General Population; Genes; Holter Electrocardiography; Hour; Incidence; Inflammation; Inflammatory; Inflammatory Response; Intervention; Leukocytes; Link; Measurement; Measures; Metal exposure; Metals; Methylation; MicroRNAs; Molecular Profiling; Oxidative Stress; Particulate Matter; Plasma; Population; Population Density; Prevention strategy; Public Health; Recruitment Activity; Regulator Genes; Research; Sampling; Scheme; Screening procedure; Small RNA; Source; Specimen; Testing; Time; Variant; Work; World Bank; abstracting; air monitoring; base; biological adaptation to stress; design; heart rate variability; mortality; next generation; novel; particle exposure; repository; small molecule; toxic metal; trafficking

Abstract Air pollution is a major public health concern in the US and worldwide. Exposure to air particulate matter (PM) with an aerodynamic diameter <2.5 ¿m (PM2.5) is well known to increase cardiovascular incidence and mortality. Inhaled PM2.5 induces systemic pro-inflammatory response and oxidative-stress, two major cardiovascular disease (CVD) pathways. Blood leukocyte gene expression profiling in highly PM-exposed subjects has revealed that systemic inflammatory responses are initiated through extensive gene expression shifts but mechanisms regulating the gene expression changes are largely unexplored. MicroRNAs (miRNAs) are small RNA molecules that have newly emerged as key regulators of gene expression. Inflammation and oxidative stress have been shown to alter miRNA expression, which can be controlled by their encoding gene DNA methylation status. Our preliminary data have shown that PM2.5 exposure changed the expression levels of certain miRNAs in blood leukocytes in a highly PM-exposed population. We hypothesize that PM exposure- induced oxidative stress and inflammatory response may cause blood leukocyte miRNA expression changes that regulate gene expression profiles. Gene expression alterations may then cause certain changes in circulating biomarkers and cardiovascular physiology to favor CVD development. We propose to test these hypotheses using data from the Beijing Truck Driver Air Pollution Study (BTDAS), our recently completed study in Beijing, China, one of the most polluted cities in the world. Thanks to special funding by the Italian Ministry of Scientific Research, the BTDAS was conducted shortly before the Beijing 2008 Olympic Games (June 15 to July 27, 2008). Two groups of subjects were recruited, i.e., 60 truck drivers (high exposure) and 60 indoor workers (low exposure). We collected personal PM2.5 and its toxic metal exposure data via air monitors and continuous EKG data via Holter monitors during their work hours, and blood samples at the end of work, on two independent work days with 1-2 week intervals. We propose to conduct an ancillary study to 1) identify PM2.5- and its toxic metal-related miRNA expression signatures by performing an unbiased screening of miRNAs using highly quantitative Next Generation Sequencing; 2) examine whether miRNA expression is associated with encoding gene methylation status; 3) determine whether PM-related miRNA signatures are associated with CVD measures using our already measured data on plasma inflammatory and blood clotting markers, blood pressure and EKG. Given the general public's ubiquitous exposure to air pollution, this research is of high significance. This study is designed to take full advantage of the unique specimen repository as well as previously collected data and examined measures to potentially identify novel mechanisms linking air pollution with CVD, and thus provide the potential to identify important CVD preventive strategies.

抽象的 空气污染是美国和全世界的一个主要公共卫生问题。 空气动力学直径 <2.5 ¿众所周知，m (PM2.5) 会增加心血管疾病的发病率， 吸入 PM2.5 会诱发全身促炎症反应和氧化应激，这是两个主要因素。 高度 PM 暴露的心血管疾病 (CVD) 途径。 受试者发现全身炎症反应是通过广泛的基因表达引发的 但调节基因表达变化的机制很大程度上尚未被探索。 是新近出现的作为基因表达关键调节因子的小RNA分子。 氧化应激已被证明会改变 miRNA 的表达，而这可由其编码基因控制 DNA 甲基化状态。我们的初步数据表明 PM2.5 暴露改变了表达水平。 高度 PM 暴露人群的血液白细胞中某些 miRNA 的变化。 诱导的氧化应激和炎症反应可能导致血液白细胞miRNA表达变化 调节基因表达谱的基因表达改变可能会导致某些变化。 循环生物标志物和心血管生理学有利于 CVD 的发展。 我们建议使用北京卡车司机空气污染研究 (BTDAS) 的数据来检验这些假设。 最近在中国北京（世界上污染最严重的城市之一）完成了研究。 BTDAS 由意大利科学研究部资助，在北京会议之前不久进行 2008年奥运会（2008年6月15日至7月27日）招募了两组受试者，即60名卡车司机。 （高暴露）和 60 名室内工作人员（低暴露）我们收集了个人 PM2.5 及其有毒金属。 在工作时间内通过空气监测仪获取暴露数据，通过动态心电图监测仪获取连续心电图数据，以及血液 我们建议在工作结束时每隔 1-2 周在两个独立工作日进行一次抽样。 辅助研究，1) 通过执行以下操作来识别 PM2.5- 及其有毒金属相关的 miRNA 表达特征 使用高度定量的下一代测序对 miRNA 进行无偏筛选 2) 检查是否； miRNA表达与编码基因甲基化状态相关；3)确定是否与PM相关； 使用我们已经测量的血浆数据将 miRNA 特征与 CVD 测量相关联 鉴于公众普遍存在炎症和凝血标志物、血压和心电图。 暴露于空气污染中，这项研究具有很高的意义。本研究旨在充分利用。 独特的样本库以及之前收集的数据和检查的措施，以潜在地 确定将空气污染与CVD联系起来的新机制，从而有可能确定重要的 CVD预防策略。

项目成果

Inhalable particulate matter and mitochondrial DNA copy number in highly exposed individuals in Beijing, China: a repeated-measure study.

• DOI: 10.1186/1743-8977-10-17
• 发表时间: 2013-04-29
• 期刊: Particle and fibre toxicology
• 影响因子: 10
• 作者: Hou L;Zhang X;Dioni L;Barretta F;Dou C;Zheng Y;Hoxha M;Bertazzi PA;Schwartz J;Wu S;Wang S;Baccarelli AA
• 通讯作者: Baccarelli AA

Environmental chemicals and microRNAs.

• DOI: 10.1016/j.mrfmmm.2011.05.004
• 发表时间: 2011-09-01
• 期刊: MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
• 影响因子: 2.3
• 作者: Hou, Lifang;Wang, Dong;Baccarelli, Andrea
• 通讯作者: Baccarelli, Andrea

Altered methylation in tandem repeat element and elemental component levels in inhalable air particles.

• DOI: 10.1002/em.21829
• 发表时间: 2014-04
• 期刊: ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
• 影响因子: 2.8
• 作者: Hou, Lifang;Zhang, Xiao;Zheng, Yinan;Wang, Sheng;Dou, Chang;Guo, Liqiong;Byun, Hyang-Min;Motta, Valeria;McCracken, John;Diaz, Anaite;Kang, Choong-Min;Koutrakis, Petros;Bertazzi, Pier Alberto;Li, Jingyun;Schwartz, Joel;Baccarelli, Andrea A.
• 通讯作者: Baccarelli, Andrea A.

Effects of particulate air pollution on blood pressure in a highly exposed population in Beijing, China: a repeated-measure study.

• DOI: 10.1186/1476-069x-10-108
• 发表时间: 2011-12-21
• 期刊: Environmental health : a global access science source
• 作者: Baccarelli A;Barretta F;Dou C;Zhang X;McCracken JP;Díaz A;Bertazzi PA;Schwartz J;Wang S;Hou L
• 通讯作者: Hou L

Air pollution exposure and lung function in highly exposed subjects in Beijing, China: a repeated-measure study.

• DOI: 10.1186/s12989-014-0051-7
• 发表时间: 2014-10-02
• 期刊: Particle and fibre toxicology
• 影响因子: 10
• 作者: Baccarelli AA;Zheng Y;Zhang X;Chang D;Liu L;Wolf KR;Zhang Z;McCracken JP;Díaz A;Bertazzi PA;Schwartz J;Wang S;Kang CM;Koutrakis P;Hou L
• 通讯作者: Hou L