2015 Progress Report: Cardiometabolic Effects of Exposure to Differing Mixtures and Concentrations of PM2.5 in Obese and Lean Adults

EPA Grant Number: R834797C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R834797
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Great Lakes Air Center for Integrative Environmental Research
Center Director: Harkema, Jack
Title: Cardiometabolic Effects of Exposure to Differing Mixtures and Concentrations of PM2.5 in Obese and Lean Adults
Investigators: Brook, Robert D. , Araujo, Jesus , Kaplan, Marianna J. , Oral, Elif
Institution: Michigan State University , University of California - Los Angeles , University of Michigan - Ann Arbor
Current Institution: University of Michigan - Ann Arbor , University of California - Los Angeles
EPA Project Officer: Ilacqua, Vito
Project Period: December 1, 2010 through November 30, 2015 (Extended to December 31, 2016)
Project Period Covered by this Report: August 1, 2014 through July 31,2015
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

We have elucidated the existence of an important confluence between key facets of the cardiometabolic syndrome (CMS) and fine particulate matter (PM2.5). Brief exposure to concentrated PM2.5 (fine CAP) for 2 hours has proven capable of triggering vasoconstriction, raising diastolic blood pressure (BP), and impairing vascular endothelial function (VEF) 1 day later - the latter occurring in a location-dependent manner suggesting that particle constituents/sources are important determinants of the responses. Two distinct mechanistic pathways were implicated - with altered autonomic nervous system (ANS) balance responsible for the increased BP and systemic inflammatory responses for the slower impairment in VEF. Though these findings are important as they help to explain how PM2.5might cause acute cardiovascular (CV) events, several important issues remain to be clarified. Moreover, our studies also suggest that a more-encompassing, yet unappreciated, convergence between PM2.5 and the CMS might exist. Not only could obesity enhance the susceptibility for adverse health effects induced by PM2.5 exposure, but also PM2.5 might promote the development of metabolic insulin resistance (IR), a central factor in the pathogenesis of obesity and the CMS itself (i.e., reciprocal relationship). We propose to build upon our previous research on the effect of short-term PM2.5 exposure on key facets of the CMS. The broad objectives are to investigate: (1) if exposure to fine CAP mixtures are capable of acutely instigating metabolic IR in addition to elevating diastolic BP and impairing VEF; (2) whether obesity confers enhanced susceptibility for these adverse responses; (3) details of the mechanistic pathways involved; (4) the extent and nature of the dose-response relationships even to levels below current 24-hour PM2.5 standards; and (5) if fine CAP derived from two dissimilar multi-pollutant ambient PM2.5 mixtures elicit differing CMS responses and the specific pollutants responsible. We will achieve these aims by examining the BP and VEF responses, along with additional/novel outcomes, in obese versus healthy adults induced by fine CAP exposures in two separate locals comprised of dissimilar PM2.5 mixtures (industrial/urban versus a near-roadway/residential). The concentrations of fine CAP will be varied to include levels from below 35 to above100 µg/m3. Using state-of-the-art physiological testing and novel biomarkers (including adipocytokines, HDL function, endothelial progenitor cell levels and function), the mechanisms responsible for the alterations in the CMS responses will be explored. The role of the ANS in the etiology of the BP increase and the effectiveness of a prophylactic measure, α+β adrenergic blockade, in obviating this response also will be tested. Finally, we will evaluate whether exposure to fine CAP can acutely elicit metabolic IR, the underlying cause of the CMS itself. This project addresses several RFA questions (Q) in an experimental fashion with humans exposed to real-world PM2.5, thereby providing findings of tremendous health/regulatory importance. The expected results will elucidate pivotal new insights into: the enhanced susceptibility of obese individuals (Q#3), the extent of the concentration-response relationship (Q#4), the mixtures of PM2.5 and their constituents /sources responsible (Q#2), and the mechanisms underlying the CV responses (Q#6). Finally, we will explore for the first time the evidence for a novel PM2.5 health effect (Q#6) - instigation of metabolic IR by PM2.5 mixtures - of critical health importance given the rising global epidemics of obesity and the CMS.

Progress Summary:

We completed study #1 of project 1 in entirety in June 2014. We randomized 30 study participants to CAP and FA exposures per protocol design in Dearborn (urban location). All health outcomes and exposures/monitoring were completed per study design without deviation from the protocol, pitfalls, or adverse events reportable to the IRB. The manuscript of the primary results has been completed and is currently in review (9/1/15). As described in detail in the year 4 progress report, we re-designed study #2 of project 1 to involve ambient level exposures in a panel study. We began the study #2 protocol in the summer of 2014. As of September 2015, we have completed n = 32 of the expected 50 study participants, each undergoing two separate non-scripted exposure window periods. Thus far, all health outcomes and exposure monitoring protocols have been completed per study design without deviation from the protocol, pitfalls, or adverse events reportable to the IRB.

Future Activities:

We plan to complete study #2 of project 1 during year 5; however, there may be some extension of the protocol to ensure completion of all 50 subjects into the planned 1 year no-cost extension time period. The plan is to complete all 50 subjects (two exposure periods each = 100 exposure windows). We will publish the main results of the urban CAP exposure study in Dearborn (currently in review) and complete all analyses of secondary outcomes (endothelial progenitor cells, HDL function) by the end of year 5 (December 2015). We will aim to complete all analyses and submit final manuscripts of the study #2 by the end of the 1 year no-cost extension (December 2016).


Journal Articles on this Report : 8 Displayed | Download in RIS Format

Other subproject views: All 17 publications 13 publications in selected types All 13 journal articles
Other center views: All 147 publications 71 publications in selected types All 71 journal articles
Type Citation Sub Project Document Sources
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)
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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)
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  • Journal Article Brook RD, Bard RL, Morishita M, Dvonch JT, Wang L, Yang HY, Spino C, Mukherjee B, Kaplan MJ, Yalavarthi S, Oral EA, Ajluni N, Sun Q, Brook JR, Harkema J, Rajagopalan S. Hemodynamic, autonomic, and vascular effects of exposure to coarse particulate matter air pollution from a rural location. Environmental Health Perspectives 2014;122(6):624-630. R834797 (2013)
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  • Journal Article Giorgini P, Rubenfire M, Das R, Gracik T, Wang L, Morishita M, Bard RL, Jackson EA, Fitzner CA, Ferri C, Brook RD. Higher fine particulate matter and temperature levels impair exercise capacity in cardiac patients. Heart 2015;101(16):1293-1301. R834797 (2014)
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  • Journal Article Giorgini P, Rubenfire M, Das R, Gracik T, Wang L, Morishita M, Bard RL, Jackson EA, Fitzner CA, Ferri C, Brook RD. Particulate matter air pollution and ambient temperature: opposing effects on blood pressure in high-risk cardiac patients. Journal of Hypertension 2015;33(10):2032-2038. R834797 (2014)
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  • Journal Article Maiseyeu A, Yang H-Y, Ramanathan G, Yin F, Bard RL, Morishita M, Dvonch JT, Wang L, Spino C, Mukherjee B, Badgeley MA, Barajas-Espinosa A, Sun Q, Harkema J, Rajagopalan S, Araujo JA, Brook RD. No effect of acute exposure to coarse particulate matter air pollution in a rural location on high-density lipoprotein function. Inhalation Toxicology 2014;26(1):23-29. R834797 (2014)
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  • Journal Article Morishita M, Bard RL, Kaciroti N, Fitzner CA, Dvonch T, Harkema JR, Rajagopalan S, Brook RD. Exploration of the composition and sources of urban fine particulate matter associated with same-day cardiovascular health effects in Dearborn, Michigan. Journal of Exposure Science & Environmental Epidemiology 2015;25(2):145-152. R834797 (2014)
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  • Journal Article Morishita M, Bard RL, Wang L, Das R, Dvonch JT, Spino C, Mukherjee B, Sun Q, Harkema JR, Rajagopalan S, Brook RD. The characteristics of coarse particulate matter air pollution associated with alterations in blood pressure and heart rate during controlled exposures. Journal of Exposure Science & Environmental Epidemiology 2015;25(2):153-159. R834797 (2014)
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  • Supplemental Keywords:

    Human exposures, susceptible populations, acute cardiovascular effects, particulate matter, human exposures, cardiometabolic syndrome, 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, acute cardiovascualr effects, human exposure, physiology, cardiopulmonary, cardiotoxicity, acute exposure

    Relevant Websites:

    GLACIER: Great Lakes Air Center for Integrated Environmental Research Exit

    Progress and Final Reports:

    Original Abstract
  • 2011 Progress Report
  • 2012 Progress Report
  • 2013 Progress Report
  • 2014 Progress Report
  • 2016 Progress Report
  • Final Report

  • Main Center Abstract and Reports:

    R834797    Great Lakes Air Center for Integrative Environmental Research

    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