2013 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: 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, 2012 through July 31,2013
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 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 PM2.5 might 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 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 2 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 2 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 will also 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:

There have been no changes in study investigators or personnel during years 1-3. As detailed in the year 2 report, the timeline and study protocol were modified to better overlap with the aims of projects 2-3. During years 1-2 (Project 1; study #1), the project was modified to perform human coarse CAP exposures at a rural site (Dexter MI) and an urban site (Dearborn MI). From the time period ending at 6/30/13, 32 subjects completed the protocol at Dexter. Thirty subjects received exposures to both filtered air (FA) and rural coarse CAP at Dexter in a randomized blinded crossover fashion. Two subjects elected to not complete a second exposure due to personal issues unrelated to the study. Thus, we completed a total of 62 exposures at Dexter by the end of study year 2. During year 3 (6/30/12 to 7/31/13) we transported the coarse CAP exposure facility (AirCARE-2) to Dearborn MI to begin urban coarse PM exposures. The facility was established at the site (e.g., electrical and power couplings) and the concentrator system was tested and validated as properly functioning prior to human studies. We began urban coarse CAP exposures after the end of winter season in April 2013. Exposures continued until the end of May 2013. Exposures were put on hold from June until Sept 2013 (planned date) as personnel were required to complete animal exposures for study 2 during this time. We completed exposures for 11 subjects at Dearborn during this time period.

Future Activities:

We will recommence human exposures to urban coarse CAP at Dearborn in September 2013. To accord with the rural exposure study results, we will complete enrollment of a minimum of 32 subjects (receiving both urban CAP and filtered air exposures) during the period of Sept 2013 to early spring 2014. We will complete analyses of our study outcomes during this time period as well. We then begin study 2 in the summer of 2014 (start of year 5). In addition to the manuscripts listed above, we have 2 papers currently in review, and 2 additional papers in preparation as of July 2013. We will complete these papers and subsequently analyze and finish abstracts and manuscripts pertaining to urban coarse CAP during year 4.


Journal Articles on this Report : 5 Displayed | Download in RIS Format

Other subproject views: All 17 publications 13 publications in selected types All 13 journal articles
Other center views: All 146 publications 69 publications in selected types All 69 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)
R834797 (2014)
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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)
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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)
    R834797 (2014)
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    R834797C002 (2016)
    R834797C002 (Final)
    R833740 (2012)
    R833740 (Final)
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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;10:43. R834797 (2013)
    R834797 (2014)
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  • Abstract: Particle and Fibre Toxicology-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)
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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, Exposure, Health Risk Assessment, Biochemistry, Biology, Risk Assessment, ambient air quality, particulate matter, aerosol particles, susceptible populations, human exposure, physiology, acute cardiovascualr effects, 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
  • 2014 Progress Report
  • 2015 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