Grantee Research Project Results
2007 Progress Report: Effect of Diesel Exhaust Particulate Exposures on Endothelial Function in Humans: The Role of Oxidative Stress
EPA Grant Number: R830954Title: Effect of Diesel Exhaust Particulate Exposures on Endothelial Function in Humans: The Role of Oxidative Stress
Investigators: Kaufman, Joel D. , Sheppard, Lianne (Elizabeth) A. , Koenig, Jane Q. , Larson, Timothy V. , Trenga, Carol , Leotta, Daniel , Gill, Edward , Sullivan, Jeff , Yost, Michael , Chandler, Wayne
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 , Human Health
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 |
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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) |
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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) |
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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) |
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Supplemental Keywords:
Ambient air, human health, dose-response, mobile sources., RFA, Scientific Discipline, Health, Air, HUMAN HEALTH, particulate matter, air toxics, Environmental Chemistry, Health Risk Assessment, Exposure, Susceptibility/Sensitive Population/Genetic Susceptibility, Risk Assessments, mobile sources, genetic susceptability, Biology, copollutant exposures, sensitive populations, atmospheric particulate matter, engine exhaust, airway epithelial cells, cardiopulmonary responses, fine particles, PM 2.5, inhaled pollutants, acute lung injury, morbidity, diesel engines, air pollution, susceptible subpopulations, endothelial function, diesel exhaust, automotive exhaust, chronic health effects, lung inflammation, oxidant gas, particulate exposure, cardiopulmonary response, heart rate, ambient particle pollution, Acute health effects, inhaled, chronic obstructive pulmonary disease, highrisk groups, human susceptibility, diesel exhaust particles, diesel exhaust particulate, cardiotoxicity, cardiopulmonary, mortality, DEP, concentrated particulate matter, air contaminant exposure, air quality, co-pollutants, environmental hazard exposures, toxics, airborne urban contaminants, biomarker, cardiovascular diseaseRelevant Websites:
http://depts.washington.edu/envhlth/nlakeexplab/Progress and Final Reports:
Original AbstractThe 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.