Grantee Research Project Results

Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM_2.5 from Multipollutant Atmospheres in the Great Lakes Region

EPA Grant Number: R834797C002
Subproject: this is subproject number 002 , 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: Health Effects Institute (2005 — 2010)
Center Director: Greenbaum, Daniel S.
Title: Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM_2.5 from Multipollutant Atmospheres in the Great Lakes Region
Investigators: Harkema, Jack , Fink, Greg , Wagner, James
Institution: Michigan State University
EPA Project Officer: Chung, Serena
Project Period: December 1, 2010 through November 30, 2015 (Extended to December 31, 2016)
RFA: Clean Air Research Centers (2009) RFA Text | Recipients Lists
Research Category: Human Health , Air

Objective:

Our objectives in Project 2 arise out of GLACIER’s overarching hypothesis that the major air pollutants, fine particulate matter (PM_2.5) and ozone(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 factors), and 4) the interactive toxicity of PM_2.5 and O₃ co-exposure. Goals of Project 2 are to determine the cardiovascular (CV), autonomic nervous system (ANS), and airway toxicity in rats acutely exposed to concentrated ambient PM_2.5 (CAP) from distinct multipollutant atmospheres commonly found in the Great Lakes Region of the United States.

Approach:

Our studies are extensions of our previous findings that CAP-induced alterations in heart rate variability are dependent on specific PM_2.5 emission sources in distinct locations in the Great Lakes Region. We will use a mobile air research facility (AirCARE 1) that is fully equipped with inhalation toxicology and atmospheric monitoring labs to conduct toxicology studies of rats exposed to CAP derived from real-world PM2.5 in three distinct locations dominated by industrial/urban, transported/regional, or near-roadway/residential emission sources. Blood pressure, heart rate, heart rate variability and direct measurements of autonomic nerve activity will be continuously monitored during CAP and/or O₃ exposures in lean or obese rats with and without diet-induced facets of the cardiometabolic syndrome (CMS; hypertension, insulin resistance, endothelial dysfunction), respectively. Acute functional responses will be measured by radiotelemetry and will be correlated with specific PM constituents and their emission sources determined for the same highly resolved 30-minute timeframes, thereby making associations of exposure and health effects especially robust. Studies will feature novel real-time sympathetic nerve recordings during PM_2.5 and/or O₃ inhalation exposure. In addition, our project will highlight the unique integrative capabilities of our research team to link specific health cardiovascular effects in a sensitive obese population with PM content by a combined technological expertise that is unavailable elsewhere. Our GLACIER project will extend and complement the research of lean and obese human subjects (Project 1), conducted at the same exposure sites, by making invasive and prolonged measurements that could not be practically or ethically done in humans (e.g., repeated CAP exposures, continuous recordings of CV and autonomic nerve function, and microscopic examination of multiple organs for exposure-related pathology). Our acute animal studies will also overlap and integrate scientifically with the animal toxicology study of long-term air pollutant exposure in Project 3, where similar endpoints will be compared.

Expected Results:

Our research has the potential to identify potentially harmful effects of exposures to specific PM_2.5 components, emission sources, and O₃ to cardiovascular function. It will also provide mechanistic evidence for the dysregulation of normal cardiovascular and metabolic pathways that leads to acute morbidity and mortality of obese individuals (susceptible population) exposed to PM_2.5 and/or O₃.

Publications and Presentations:

Publications have been submitted on this subproject: View all 73 publications for this subproject | View all 148 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 28 journal articles for this subproject | View all 72 journal articles for this center

Supplemental Keywords:

inhalation toxicology, acute multipollutant exposure, obesity, rats,, Air, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Health Risk Assessment, Biology, Biochemistry, air toxics, Risk Assessment, aerosol particles, human health, physiology, human exposure, particulate matter, cardiotoxicity, susceptible populations, acute cardiovascualr effects, ambient air quality, cardiopulmonary

Progress and Final Reports:

Main Center Abstract and Reports:

R834797 Health Effects Institute (2005 — 2010)

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 PM_2.5 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.