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球的主要公共卫生问题。暴露于空气颗粒物（PM） 众所周知，具有空气动力学直径<2.5？（PM2.5），会增加心血管的发生率和 死亡。吸入的PM2.5诱导全身性促炎反应和氧化压力，两个主要 心血管疾病（CVD）途径。高度PM暴露的血液白细胞基因表达谱分析 受试者表明，全身性炎症反应是通过广泛的基因表达开始的 转移但调节基因表达变化的机制在很大程度上是出乎意料的。 microRNA（mirnas） 是小的RNA分子，新出现为基因表达的关键调节剂。发炎和 氧化应激已显示出改变miRNA表达，可以通过其编码基因控制 DNA甲基化状态。我们的初步数据表明，PM2.5暴露改变了表达式水平 在高度PM暴露的人群中，血清细胞中某些miRNA。我们假设PM暴露 - 诱导的氧化应激和炎症反应可能导致血清细胞miRNA表达变化 调节基因表达谱。然后，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开发。 我们建议使用来自北京卡车驾驶员空气污染研究（BTDAS）的数据来检验这些假设 最近在中国北京完成的研究是世界上污染最严重的城市之一。感谢特别 意大利科学研究部的资助，BTDA是在北京前不久进行的 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个卡车司机 （高暴露）和60名室内工人（低暴露）。我们收集了个人PM2.5及其有毒金属 通过空中显示器和连续的心电图数据在工作时间和血液中通过Holter监视器进行曝光数据 在工作结束时，在两个独立的工作日，间隔为1-2周。我们建议进行 辅助研究至1）通过执行 使用高定量的下一代测序对miRNA进行公正筛查； 2）检查是否 miRNA表达与编码基因甲基化状态有关。 3）确定是否与PM相关 miRNA签名使用我们已经测量的血浆数据与CVD测量有关 炎症和血液服装标记，血压和心电图。鉴于公众无处不在 暴露于空气污染，这项研究具有很高的意义。这项研究旨在充分利用 独特的标本存储库以及先前收集的数据并检查了措施 确定将空气污染与CVD联系起来的新型机制，从而提供了识别重要的潜力 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