Impact/Purpose:

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.

Description:

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.

URLs/Downloads:

2012 Progress Report

2013 Progress Report

2011 Progress Report

Record Details:

Record Type:PROJECT( ABSTRACT )

Start Date:12/01/2010

Completion Date:11/30/2015

Record ID: 248943

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Related Organizations:

Role :OWNER

Organization Name :LOVELACE RESPIRATORY RESEARCH INSTITUTE

Organization Name :UW CCAR

Mailing Address :2425 Ridgecrest Dr. SE

Citation :Albuquerque

State :NM

Zip Code :87108



Role :OWNER

Organization Name :UNIVERSITY OF WASHINGTON

Organization Name :UW CCAR

Mailing Address :1410 NE Campus Parkway

Citation :Seattle

State :WA

Zip Code :98195

Project Information:

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.

Cost :$940,545.00

Research Component :Health Effects

Project IDs:

ID Code :R834796C004

Project type :Center