Grantee Research Project Results

Vascular Response to Traffic-Derived Inhalation in Humans

EPA Grant Number: R834796C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R834796
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Predictive Toxicology Center for Organotypic Cultures and Assessment of AOPs for Engineered Nanomaterials
Center Director: Faustman, Elaine
Title: Vascular Response to Traffic-Derived Inhalation in Humans
Investigators: Kaufman, Joel D. , Larson, Timothy V. , MacDonald, Jacob , Rosenfeld, Michael
Current Investigators: Kaufman, Joel D. , Larson, Timothy V.
Institution: University of Washington , Lovelace Biomedical & Environmental Research Institute
Current Institution: University of Washington
EPA Project Officer: Callan, Richard
Project Period: December 1, 2010 through November 30, 2015 (Extended to November 30, 2017)
RFA: Clean Air Research Centers (2009) RFA Text | Recipients Lists
Research Category: Human Health , Air

Objective:

Air pollution exposures are associated with ischemic heart diseases. Recent observations demonstrate that traffic-related air pollutants acutely trigger increased arterial reactivity, vasoconstriction, and increased blood pressure in humans and animals; these effects can be used to understand both acute and chronic health effects of air pollutants. This project will use controlled clinical exposures to test the hypothesis that traffic-derived (e.g., diesel and gasoline engine) aerosols exert vascular effects in human subjects, and provide insight into the most toxic components and underlying mechanisms.

Approach:

We will use a well-characterized human exposure facility, customized to reflect findings in Center Projects 1-3, to examine effects of simulated roadway-derived exhaust in a double-blind, randomized, controlled crossover experiment. Building on data derived from animal studies and exposure characterization studies (Projects 1-3) in Center years 1 and 2, we propose clinical experiments nested within a crossover trial to be largely conducted in Center years 3 and 4. In healthy subjects, we will test whether a traffic-derived laboratory-generated high-potency pollution atmosphere, as suggested through other Center projects, causes an increased vascular response (brachial artery vasoconstriction and increased blood pressure) compared with both a roadway-derived exposure of hypothesized lower potency and with filtered air.

We also propose several nested aims to examine hypotheses in healthy volunteers in order to better understand the epidemiological observations of both acute (triggering) and chronic (pro-atherogenic) air pollution effects. These nested aims include: whether specific exhaust-related monocytic gene expression effects are mediated by lipid peroxidation and blocked by an anti-oxidant; whether traffic-related pollutants’ vasoconstrictive effects are increased in subjects with a common SNP variant in the gene coding for lipoxygenase-15; and whether lymphocyte DNA hypermethylation in specific genes is increased with exposure to simulated roadway-derived exposures.

Expected Results:

By coordinating closely with Center Projects 1-3, we will determine whether specific aspects of traffic-derived exposure (primary vs. secondary organics, particulate vs. gases, spark-ignition vs. diesel engine vs. a mixture) enhance the human vascular response to pollutants. We also will learn about biological mechanisms involved in human health effects from traffic pollutants. These studies will have important implications for air pollution regulatory efforts and suggest new approaches for the prevention of cardiovascular health effects.

Publications and Presentations:

Publications have been submitted on this subproject: View all 2 publications for this subproject | View all 197 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 2 journal articles for this subproject | View all 93 journal articles for this center

Supplemental Keywords:

cardiovascular health, particulate matter, motor vehicle,, Health, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, Air Quality, air toxics, Health Risk Assessment, Risk Assessments, mobile sources, Biochemistry, Risk Assessment, ambient air quality, atmospheric particulate matter, particulate matter, aerosol particles, air pollutants, motor vehicle emissions, vehicle emissions, air quality models, motor vehicle exhaust, airway disease, bioavailability, air pollution, particle exposure, atmospheric aerosols, ambient particle health effects, vascular dysfunction, cardiotoxicity, atmospheric chemistry, exposure assessment

Progress and Final Reports:

Main Center Abstract and Reports:

R834796 Predictive Toxicology Center for Organotypic Cultures and Assessment of AOPs for Engineered Nanomaterials

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834796C001 Exposure Mapping – Characterization of Gases and Particles for ExposureAssessment in Health Effects and Laboratory Studies
R834796C002 Simulated Roadway Exposure Atmospheres for Laboratory Animal and Human Studies
R834796C003 Cardiovascular Consequences of Immune Modification by Traffic-Related Emissions
R834796C004 Vascular Response to Traffic-Derived Inhalation in Humans
R834796C005 Effects of Long-Term Exposure to Traffic-Derived Particles and Gases on Subclinical Measures of Cardiovascular Disease in a Multi-Ethnic Cohort

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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.