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.

Public Health Relevance

Lay summary Air pollution is a well known contributor to cardiovascular disease (CVD) and death but the underlying mechanisms remain poorly understood. Traffic is a major source of air pollution and due to the general public's unavoidable exposure;this research has important and far-reaching public health implications. This study is designed to identify novel mechanisms related to miRNAs, small molecules that are newly discovered to control gene expression, linking air pollution with CVD. Analysis of data from a highly air pollution-exposed population in Beijing, China, will have the potential to identify mechanisms that may not be detectable in a low exposed population, thus providing the groundwork to develop important novel preventive strategies for future potential CVD intervention efforts.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Tyson, Frederick L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northwestern University at Chicago
Public Health & Prev Medicine
Schools of Medicine
United States
Zip Code
Nwanaji-Enwerem, Jamaji C; Colicino, Elena; Trevisi, Letizia et al. (2016) Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study. Environ Epigenet 2:
Hou, Lifang; Barupal, Jitendra; Zhang, Wei et al. (2016) Particulate Air Pollution Exposure and Expression of Viral and Human MicroRNAs in Blood: The Beijing Truck Driver Air Pollution Study. Environ Health Perspect 124:344-50
Lin, Vania W; Baccarelli, Andrea A; Burris, Heather H (2016) Epigenetics-a potential mediator between air pollution and preterm birth. Environ Epigenet 2:
Colicino, Elena; Giuliano, Giulia; Power, Melinda C et al. (2016) Long-term exposure to black carbon, cognition and single nucleotide polymorphisms in microRNA processing genes in older men. Environ Int 88:86-93
Liu, Cong; Xu, Junhui; Chen, Yahong et al. (2015) Characterization of genome-wide H3K27ac profiles reveals a distinct PM2.5-associated histone modification signature. Environ Health 14:65
Sanchez-Guerra, Marco; Zheng, Yinan; Osorio-Yanez, Citlalli et al. (2015) Effects of particulate matter exposure on blood 5-hydroxymethylation: results from the Beijing truck driver air pollution study. Epigenetics 10:633-42
Guo, Liqiong; Byun, Hyang-Min; Zhong, Jia et al. (2014) Effects of short-term exposure to inhalable particulate matter on DNA methylation of tandem repeats. Environ Mol Mutagen 55:322-35
Baccarelli, Andrea A; Zheng, Yinan; Zhang, Xiao et al. (2014) Air pollution exposure and lung function in highly exposed subjects in Beijing, China: a repeated-measure study. Part Fibre Toxicol 11:51
Hou, Lifang; Zhang, Xiao; Zheng, Yinan et al. (2014) Altered methylation in tandem repeat element and elemental component levels in inhalable air particles. Environ Mol Mutagen 55:256-65
Burris, Heather H; Baccarelli, Andrea A (2014) Environmental epigenetics: from novelty to scientific discipline. J Appl Toxicol 34:113-6

Showing the most recent 10 out of 24 publications