Grantee Research Project Results
Cardiometabolic Effects of Exposure to Differing Mixtures and Concentrations of PM2.5 in Obese and Lean Adults
EPA Grant Number: R834797C001Subproject: 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: Center for Research on Early Childhood Exposure and Development in Puerto Rico
Center Director: Alshawabkeh, Akram
Title: Cardiometabolic Effects of Exposure to Differing Mixtures and Concentrations of PM2.5 in Obese and Lean Adults
Investigators: Brook, Robert D. , Kaplan, Marianna J. , Oral, Elif , Araujo, Jesus
Institution: University of Michigan , University of California - Los Angeles
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:
We have discovered an important interaction between key aspects of the cardio-metabolic syndrome (CMS) and exposure to fine particulate matter (PM2.5). Brief exposure to concentrated ambient PM2.5 (CAP) for 2 hours triggers arterial narrowing(vasoconstriction), increased diastolic blood pressure (BP), and impairment of proper blood vessel function (vascular endothelial function (VEF)) 1 day after exposure – the latter occurring in a location-dependent manner suggesting that particle constituents are important determinants of these health effects caused by multipollutant exposures. Two pathways were implicated in these responses - 1) changes in autonomic nervous system (ANS) balance responsible for the increased BP and 2) systemic inflammatory responses for the slower impairment in VEF. Though these findings help us understand how PM2.5 might cause acute cardiovascular (CV) changes, several important issues remain to be clarified. Moreover, our previous studies also suggest that a moreencompassing, yet unappreciated, convergence might exist between PM2.5 exposure and the CMS. Not only could obesity enhance the susceptibility to 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 cause of obesity and the CMS itself. Our objectives are to investigate: 1) if exposure to 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 responses; 3) details of the mechanisms responsible for health effects; 4) the nature of the dose-response relationships even at concentrations below current 24-hour PM2.5 standards; and 5) if CAP derived from 2 dissimilar multipollutant ambient PM2.5 atmospheres cause differing CMS responses and the specific pollutants responsible.
Approach:
We will achieve these aims by examining the BP and VEF responses, along with additional outcomes, in obese versus lean adults, caused by CAP exposures in 2 separate locals comprised of dissimilar PM2.5 mixtures (industrial/urban versus a near-roadway/residential). The concentrations of CAP will be varied to include levels from below 35 to above 100 μg/m3. Using state-of-the-art physiological testing and biomarkers, the mechanisms responsible for the alterations in CMS responses will be explored. The role of the ANS in the BP increase and the effectiveness of a prophylactic measure, α+β adrenergic blockade, in preventing this response will also be tested. Finally, we will evaluate whether exposure to CAP can acutely elicit metabolic IR.
Expected Results:
This project will address questions with humans exposed to real-world PM2.5, thereby providing findings of tremendous public health importance. The expected results will elucidate new insights into: the susceptibility of obese individuals to multipollutant atmospheric exposures, the extent of concentration-response relationships, the mixtures of PM2.5 and their constituents responsible for health effects, and the mechanisms underlying the CV responses. Finally, we will explore the evidence for a novel PM2.5 health effect – instigation of metabolic IR.
Publications and Presentations:
Publications have been submitted on this subproject: View all 17 publications for this subproject | View all 148 publications for this centerJournal Articles:
Journal Articles have been submitted on this subproject: View all 13 journal articles for this subproject | View all 72 journal articles for this centerSupplemental Keywords:
metabolic syndrome, vascular, pollution mixtures, human subjects,, 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, acute cardiovascualr effects, human exposure, physiology, cardiopulmonary, cardiotoxicity, acute exposureProgress and Final Reports:
Main Center Abstract and Reports:
R834797 Center for Research on Early Childhood Exposure and Development in Puerto Rico 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
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.
Project Research Results
- Final Report
- 2016 Progress Report
- 2015 Progress Report
- 2014 Progress Report
- 2013 Progress Report
- 2012 Progress Report
- 2011 Progress Report
13 journal articles for this subproject
Main Center: R834797
148 publications for this center
72 journal articles for this center