2007 Progress Report: Effect of Diesel Exhaust Particulate Exposures on Endothelial Function in Humans: The Role of Oxidative Stress

EPA Grant Number: R830954
Title: Effect of Diesel Exhaust Particulate Exposures on Endothelial Function in Humans: The Role of Oxidative Stress
Investigators: Kaufman, Joel D. , Chandler, Wayne , Gill, Edward , Koenig, Jane Q. , Larson, Timothy V. , Leotta, Daniel , Sheppard, Lianne (Elizabeth) A. , Sullivan, Jeff , Trenga, Carol , Yost, Michael
Institution: University of Washington
EPA Project Officer: Chung, Serena
Project Period: August 15, 2003 through August 14, 2006 (Extended to August 14, 2008)
Project Period Covered by this Report: August 15, 2006 through August 14,2007
Project Amount: $1,036,972
RFA: Airborne Particulate Matter Health Effects: Cardiovascular Mechanisms (2002) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air , Health Effects

Objective:

Diesel exhaust particulate is a substantial and biologically active fraction of urban ambient fine particulate air pollution, which is associated with increases in cardiovascular morbidity and mortality. This project addresses the overall hypothesis that ambient fine particulate matter exerts cardiovascular health effects via alteration of endothelial homeostasis, through a mechanism mediated by oxidative stress. These studies use a controlled human inhalation exposure to diesel exhaust as an experimental model exposure for ambient fine particulate, to address the following objectives: 1) Determine whether exposure to inhaled diesel exhaust (DE) is associated with endothelial dysfunction in a concentration-related manner; 2) Determine whether exposure to inhaled DE is associated with evidence of systemic oxidative stress; and 3) Determine whether antioxidant supplementation blunts the DE effect on endothelial function.

Progress Summary:

The pilot study was completed with 9 subjects in June 2004. Results from the pilot study informed the subsequent experiments. Twenty-three subjects, including six healthy adults and 17 adults with metabolic syndrome completed Experiments 1 and 2, and from these experiments, we concluded that exposure to diesel exhaust impacts both brachial artery diameter and plasma concentrations of endothelin-1. Based on data collected in Experiments 1 and 2, the protocol for Experiment 3 was finalized and approved in May 2006. This experiment examines whether supplementation with antioxidant can alter the effect of DE on endothelial function and oxidative stress. Recruitment and enrollment into Experiment 3 is underway.

Future Activities:

Additional data analysis, particularly for Experiment 3, is ongoing.


Journal Articles on this Report : 3 Displayed | Download in RIS Format

Other project views: All 33 publications 10 publications in selected types All 10 journal articles
Type Citation Project Document Sources
Journal Article Carlsten C, Kaufman JD, Peretz A, Trenga CA, Sheppard L, Sullivan JH. Coagulation markers in healthy human subjects exposed to diesel exhaust. Thrombosis Research 2007;120(6):849-855. R830954 (2007)
R830954 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: ScienceDirect-Abstract
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  • Journal Article Peretz A, Leotta DF, Sullivan JH, Trenga CA, Sands FN, Aulet MR, Paun M, Gill EA, Kaufman JD. Flow mediated dilation of the brachial artery: an investigation of methods requiring further standardization. BMC Cardiovascular Disorders 2007;7:11 (8 pp.). R830954 (2007)
    R830954 (Final)
    R827355 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: BMC-Full Text HTML
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  • Other: BMC-Full Text PDF
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  • Journal Article Peretz A, Peck EC, Bammler TK, Beyer RP, Sullivan JH, Trenga CA, Srinouanprachnah S, Farin FM, Kaufman JD. Diesel exhaust inhalation and assessment of peripheral blood mononuclear cell gene transcription effects: an exploratory study of healthy human volunteers. Inhalation Toxicology 2007;19(14):1107-1119. R830954 (2007)
    R830954 (Final)
    R827355 (Final)
  • Abstract from PubMed
  • Abstract: Taylor&Francis-Abstract
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  • Supplemental Keywords:

    Ambient air, human health, dose-response, mobile sources., RFA, Health, Scientific Discipline, Air, HUMAN HEALTH, particulate matter, air toxics, Environmental Chemistry, Health Risk Assessment, Exposure, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, mobile sources, genetic susceptability, Biology, copollutant exposures, sensitive populations, engine exhaust, atmospheric particulate matter, cardiopulmonary responses, fine particles, morbidity, PM 2.5, airway epithelial cells, diesel engines, inhaled pollutants, acute lung injury, air pollution, automotive exhaust, diesel exhaust, susceptible subpopulations, endothelial function, cardiopulmonary response, chronic health effects, lung inflammation, oxidant gas, particulate exposure, heart rate, ambient particle pollution, Acute health effects, highrisk groups, inhaled, chronic obstructive pulmonary disease, human susceptibility, diesel exhaust particles, cardiopulmonary, cardiotoxicity, mortality, diesel exhaust particulate, acute exposure, air quality, cardiovascular disease, biomarker, toxics, concentrated particulate matter, environmental hazard exposures, air contaminant exposure, co-pollutants, airborne urban contaminants

    Relevant Websites:

    http://depts.washington.edu/envhlth/nlakeexplab/

    Progress and Final Reports:

    Original Abstract
  • 2004 Progress Report
  • 2005 Progress Report
  • 2006 Progress Report
  • Final Report