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Extramural Research

Great Lakes Air Center for Integrative Environmental Research (GLACIER)

EPA Grant Number: R834797
Center: Great Lakes Air Center for Integrative Environmental Research
Center Director: Harkema, Jack
Title: Great Lakes Air Center for Integrative Environmental Research (GLACIER)
Investigators: Harkema, Jack
Institution: Michigan State University , The Ohio State University - Main Campus , University of California - Los Angeles , University of Michigan - Ann Arbor
EPA Project Officer: Peffers, Mel
Project Period: January 1, 2011 through December 31, 2015
Project Amount: $7,999,875
RFA: Clean Air Research Centers (2009)
Research Category: Health Effects

Description:

Objective:

GLACIER is a multidisciplinary center with the objective to explore one of the most prevalent and important global health-environment interfaces: the interrelationships between facets of the cardiometabolic syndrome (CMS) and air pollution. CMS is among the leading causes of death and threats to worldwide health. In tandem, exposure to air pollution, most notably fine particle matter (PM2.5), remains highly prevalent and ranks among the leading causes of global mortality. Inter-relationships and health impacts of this burgeoning confluence between these two epidemics are of tremendous importance to elucidate. Our previous research has elucidated that PM2.5 exposure plays a critical, yet under-appreciated, role in eliciting or exacerbating several key facets of the CMS-including elevating blood pressure, impairing vascular function, and even worsening metabolic insulin sensitivity and adiposity over a chronic duration. We have also found that the location of exposure, multipollutant context, and constituents within PM2.5 affect the responses. The full extent and importance of inter-relationships between CMS and air pollution, individual susceptibility, specific pollution components, multipollutant atmospheres, PM2.5 - ozone (O3) coexposures, and underlying mechanisms of toxicity are all key issues remaining to be clarified. Our center’s overall hypothesis is that PM2.5 and O3 are 1) capable of eliciting multiple important adverse cardiometabolic health effects that are dependent on 2) the local multipollutant milieu, 3) an individual’s pre-existing cardiovascular (CV) and metabolic condition (susceptibility), and 4) the interactive toxicity of PM2.5 and O3 coexposure.

Approach:

In conjunction with core facilities, GLACIER consists of 3 controlled exposure projects that each addresses specific aspects of the CMS-air pollution interface. The projects are scientifically integrated and interactive which will foster synergistic insights and cohesive synthesis of conclusions. The Exposure Characterization Core (ECC) is an integral part of all three Projects of the Great Lakes Air Center for Integrative Environmental Research (GLACIER). In coordination with and support of the GLACIER Research Projects, the ECC will provide measurements of multi-pollutant exposures for both human subject (Project 1) and animal toxicology (Projects 2 and 3) studies. The overall objectives of the ECC are to 1) determine the mass, size, and chemical composition of pollutants for each exposure period, 2) determine the atmospheric emission sources responsible for the observed exposure concentrations, and 3) provide a detailed assessment of the differences in air pollution composition, sources, and chemistry between each of the exposure sites across each of the Projects. The objectives of the GLACIER BDMC are to provide guidance for the statistical design and analysis of studies and data management services that allow for the integration of the data into a single platform that facilitates timely analysis for GLACIER investigators and projects. Specific aims for this Core are (1) to assist GLACIER investigators with statistical and data aspects of their research by providing expertise in the design, conduct and analysis of studies in Projects 1-3; (2) to establish a database for each project on a secure computerized system; and (3) to implement a website to allow data import and export in a secured, controlled environment with a user-friendly interface.

Project 1 aims to elucidate in humans the mechanisms of adverse CMS responses and the concentration-response relationships of acute exposures to differing PM2.5 mixtures.

Project 2 aims to determine the short-term CV, autonomic and airway toxicity in rats exposed to differing PM2.5 mixtures.

Project 3 expands upon the main theme by determining the CMS toxicity of differing longer-term exposures in mice. Each project will also investigate the role of pre-existing susceptibility and the comparative effects of PM2.5 mixtures derived from 2-3 dissimilar multipollutant milieus of regional importance (near-roadway, industrial, transported). Toxic effects of PM2.5, O3, each alone and in combination, will be evaluated at each location.

Expected Results:

We will address 1) temporal-response relationships to pollutant exposure and the development of CMS, 2) CMS effects of ozone and fine particle mixtures from 3 differing locations and their interactive toxicity, 3) the role of obesity and pre-existing cardiometabolic abnormalities in individual susceptibility, 4) concentration-response relationships for particles and O3; and 5) mechanisms whereby air pollutants elicit CV and metabolic health effects. Our results will provide critical insights into the health effects of PM2.5, O3, and their coexposures in a multipollutant context.


Journal Articles: 13 Displayed | Download in RIS Format

Other center views: All 40 publications 13 publications in selected types All 13 journal articles

Type Citation Sub Project Document Sources
Journal Article Balasubramanian P, Sirivelu MP, Weiss KA, Wagner JG, Harkema JR, Morishita M, Mohankumar PS, Mohankumar SM. Differential effects of inhalation exposure to PM 2.5 on hypothalamic monoamines and corticotrophin releasing hormone in lean and obese rats. NeuroToxicology 2013;36(May 2013):106-111. R834797 (2013)
R834797C002 (2012)
R834797C002 (2013)
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  • Journal Article Blazek A, Rutsky J, Osei K, Maiseyeu A, Rajagopalan S. Exercise-mediated changes in high-density lipoprotein: impact on form and function. American Heart Journal 2013;166(3):392-400. R834797 (2013)
    R834797C003 (2013)
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  • Abstract: American Heart Journal-Abstract
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  • Journal Article Brook RD, Rajagopalan S. What you breathe trigger a stroke within hours? comment on "ambient air pollution and the risk of acute ischemic stroke". Archives of Internal Medicine 2012;172(3):235-236. R834797C003 (2012)
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  • Journal Article Brook RD, Bard RL, Kaplan MJ, Yalavarthi S, Morishita M, Dvonch JT, Wang L, Yang H-Y, Spino C, Mukherjee B, Oral EA, Sun Q, Brook JR, Harkema J, Rajagopalan S. The effect of acute exposure to coarse particulate matter air pollution in a rural location on circulating endothelial progenitor cells: results from a randomized controlled study. Inhalation Toxicology 2013;25(10):587-592. R834797 (2013)
    R834797C001 (2013)
    R834797C002 (2013)
    R834797C003 (2013)
    R833740 (2012)
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  • Journal Article Brook RD, Xu X, Bard RL, Dvonch JT, Morishita M, Kaciroti N, Sun Q, Harkema J, Rajagopalan S. Reduced metabolic insulin sensitivity following sub-acute exposures to low levels of ambient fine particulate matter air pollution. The Science of the Total Environment 2013;448:66-71. R834797 (2012)
    R834797 (2013)
    R834797C001 (2012)
    R834797C001 (2013)
    R834797C002 (2012)
    R834797C002 (2013)
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  • Journal Article Liu C, Ying Z, Harkema J, Sun Q, Rajagopalan S. Epidemiological and experimental links between air pollution and type 2 diabetes. Toxicologic Pathology 2013;41(2):361-373. R834797 (2013)
    R834797C002 (2012)
    R834797C002 (2013)
    R834797C003 (2013)
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  • Journal Article Sun L, Liu C, Xu X, Ying Z, Maiseyeu A, Wang A, Allen K, Lewandowski RP, Bramble LA, Morishita M, Wagner JG, Dvonch JT, Sun Z, Yan X, Brook RD, Rajagopalan S, Harkema JR, Sun Q, Fan Z. Ambient fine particulate matter and ozone exposures induce inflammation in epicardial and perirenal adipose tissues in rats fed a high fructose diet. Particle and Fibre Toxicology 2013;10(1):43. R834797 (2013)
    R834797C001 (2013)
    R834797C002 (2013)
    R834797C003 (2013)
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  • Full-text: Particle and Fibre Toxicology-Full Text HTML
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  • Abstract: Particle and Fibre Toxicology-Abstract
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  • Journal Article Wold LE, Ying Z, Hutchinson KR, Velten M, Gorr MW, Velten C, Youtz DJ, Wang A, Lucchesi PA, Sun Q, Rajagopalan S. Cardiovascular remodeling in response to long-term exposure to fine particulate matter air pollution. Circulation Heart Failure 2012;5(4):452-461. R834797C003 (2012)
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  • Full-text: American Heart Association - Full text HTML
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  • Journal Article Xu X, Liu C, Xu Z, Tzan K, Wang A, Rajagopalan S, Sun Q. Altered adipocyte progenitor population and adipose-related gene profile in adipose tissue by longterm high-fat diet in mice. Life Sciences 2012;90(25-26):1001-1009. R834797C003 (2012)
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  • Journal Article Ying Z, Xu X, Chen M, Liu D, Zhong M, Chen L-C, Sun Q, Rajagopalan S. A synergistic vascular effect of airborne particulate matter and nickel in a mouse model. Toxicological Sciences 2013;135(1):72-80. R834797 (2013)
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  • Journal Article Pancras JP, Landis MS, Norris GA, Vedantham R, Dvonch JT. Source apportionment of ambient fine particulate matter in Dearborn, Michigan, using hourly resolved PM chemical composition data. The Science of the Total Environment 2013;448:2-13. R834797 (2013)
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  • Abstract: Science Direct-Abstract
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  • Journal Article Wagner JG, Allen K, Yang HY, Nan B, Morishita M, Mukherjee B, Dvonch JT, Spino C, Fink GD, Rajagopalan S, Sun Q, Brook RD, Harkema JR. Cardiovascular depression in rats exposed to inhaled particulate matter and ozone: effects of diet-induced metabolic syndrome. Environmental Health Perspectives 2014;122(1):27-33. R834797 (2013)
    R834797C001 (2013)
    R834797C002 (2013)
    R834797C003 (2013)
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  • Journal Article Ying Z, Xu X, Bai Y, Zhong J, Chen M, Liang Y, Zhao J, Liu D, Morishita M, Sun Q, Spino C, Brook RD, Harkema JR, Rajagopalan S. Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of sympathetic nervous system: a role for hypothalamic inflammation. Environmental Health Perspectives 2014;122(1):79-86. R834797 (2013)
    R834797C002 (2013)
    R834797C003 (2013)
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  • Abstract from PubMed
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  • Supplemental Keywords:

    Multipollutant, PM2.5, O3, cardiometabolic syndrome, Great Lakes,, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, air toxics, Health Risk Assessment, Exposure, Biochemistry, Biology, Risk Assessment, ambient air quality, particulate matter, aerosol particles, susceptible populations, human exposure, physiology, acute cardiovascualr effects, cardiopulmonary, cardiotoxicity, acute exposure

    Progress and Final Reports:
    2011 Progress Report
    2012 Progress Report
    2013 Progress Report

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834797C001 Cardiometabolic Effects of Exposure to Differing Mixtures and Concentrations of PM2.5 in Obese and Lean Adults
    R834797C002 Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM2.5 from Multipollutant Atmospheres in the Great Lakes Region
    R834797C003 Long Term Metabolic Consequences of Exposures to Multipollutant Atmospheres in the Great Lakes Region

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    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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