Grantee Research Project Results
2004 Progress Report: Coronary Effects of Combustion-Source Particulate Matter
EPA Grant Number: R830839Title: Coronary Effects of Combustion-Source Particulate Matter
Investigators: Campen, Matthew J.
Current Investigators: Campen, Matthew J. , McDonald, Jacob D. , Reed, Matthew D.
Institution: Lovelace Biomedical & Environmental Research Institute
EPA Project Officer: Chung, Serena
Project Period: April 21, 2003 through April 20, 2006 (Extended to March 31, 2007)
Project Period Covered by this Report: April 21, 2004 through April 20, 2005
Project Amount: $1,018,920
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:
We have conducted several exposures with both the ApoE-/- and C57BL/6J with diesel exhaust, as well as a brief study with road dust. The first manuscript from this project has been accepted to Toxicological Sciences, and is included as an appendix. Several abstracts have been submitted, and we are awaiting the decisions by the American Heart Association and the upcoming Nanoparticle Meeting in Durham, NC; we presented a poster on these studies at this year’s Society of Toxicology meeting.
Progress Summary:
ApoE-/- mice fed on a high fat diet for 16 weeks were exposed to diesel exhaust with and without particles and to road dust. Particulate mass concentrations were 500 and 3500 μg/m3. Telemetric recordings of ECG were made continuously throughout the studies.
Coronary vessels were isolated and exposed to the saline-soluble constituents in diesel exhaust and assayed for constrictive (Endothelin-1) and dilatory (Sodium nitroprusside) function.
Summary of Findings: The manuscript, “Nonparticulate Components of Diesel Exhaust Promote Constriction in Coronary Arteries from ApoE-/- Mice” contains results from the present grant and is appended as the primary report of findings for the present year. To summarize the findings, the vapor phase of the whole exhaust drove several pathophysiological effects in the ApoE-/-, but not C57BL/6J mice. Most importantly, electrocardiographic signs consistent with myocardial ischemia were observed in whole-body exposed mice. The presence or absence of particles did not change the ultimate response, implicating constituents of the vapor phase as the driving agent(s). In ex vivo studies, vapor phase constituents of diesel exhaust promoted an enhancement of coronary constriction to endothelin and a reduction in the dilatory response to a nitric oxide donor, sodium nitroprusside.
Effects of particles on pulmonary injury were clear. Particles in both diesel exhaust and road dust caused some amount of increase in of lavageable cellularity. The vapor phase of the whole exhaust did not create such inflammation, even at the highest concentrations. Additionally, C57BL/6J mice did not show any electrocardiographic effects from diesel exhaust, with or without particles.
Future Activities:
For the final year of the project, we have decided to expand the study in three directions. First, we are interested in the compounds which drive the vascular tendency towards constriction. Second, since particles did not seem to play a role in the cardiovascular events (neither diesel nor road dust), we are planning an experiment with a gasoline exhaust exposure system, which releases primarily gases and very low particle levels, which we will use to compare against road dust, that has no gases. Third, since we had evidence of elevated oxidized Low Density Lipoproteins (oxLDL), we wanted to observe the chronic impact on the promotion of the atherosclerotic lesions, and so we are currently exposing a cohort of ApoE-/- mice to gasoline exhaust. The gasoline system will be shut down by the end of the year, so we felt it would be best to do this study first, then revisit the chronic diesel exposures.
The primary reason for expanding in these new directions is to better understand the importance of some of our findings. We have, at least cursorily, addressed all of our specific aims with notable success. We have a great deal of data that will require further analysis for heart rate variability, and many tissues that will be assayed by immunohistochemistry to characterize the level of atherosclerotic disease in the ApoE-/- mice. Clearly, more detail needs to be included in the ex vivo studies to identify the driving components of the vapor phase and the dosimetric issues of these rapidly metabolized compounds (formaldehyde, alkanes, etc.). Through collaborations with other investigators, we have identified genes that may be upregulated, including monocyte chemotactic protein (MCP), and we wish to assay specifically for those gene products in our stored tissues.
Personnel: The essential personnel for this study remain involved (Campen, McDonald). Our affiliation with the Department of Surgery at UNM has yielded the support of two Cardiothoracic Surgical trainees, Drs. Andrew Helms and Sathish Babu. Also, Drs. Ben Walker and Nancy Kanagy have consulted on the isolated vessel techniques and provided training resources for myself and my staff. Selita Lucas and Lee Blair have been assigned as the primary technicians for this project. We are bringing in a post-doctoral trainee, Dr. Amie Lund, at the end of August, and 50% of her support for the 1st few months will come from this grant. She will be interacting with both Dr. Vernon Walker and me to develop mitochondrial toxicity assays for vascular tissue, which will be used in the previously obtained aortas from earlier diesel exposures, plus ongoing gasoline exhaust exposures.
Journal Articles on this Report : 1 Displayed | Download in RIS Format
Other project views: | All 22 publications | 6 publications in selected types | All 6 journal articles |
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Type | Citation | ||
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Campen MJ, Babu NS, Helms GA, Pett S, Wernly J, Mehran R, McDonald JD. Nonparticulate components of diesel exhaust promote constriction in coronary arteries from ApoE-/-mice. Toxicological Sciences 2005;88(1):95-102. |
R830839 (2004) R830839 (2005) R830839 (Final) |
Exit Exit |
Supplemental Keywords:
RFA, Scientific Discipline, Health, Air, TREATMENT/CONTROL, particulate matter, Air Pollution Control, Health Risk Assessment, air toxics, Risk Assessments, Incineration/Combustion, copollutant exposures, elderly adults, health effects, atmospheric particulate matter, airway epithelial cells, cardiopulmonary responses, fine particles, combustion-related pollutants, stratospheric ozone, acute cardiovascular effects, acute lung injury, vascoconstriction, combustion emissions, air pollution, susceptible subpopulations, cardiac arrest, chronic health effects, lung inflammation, oxidant gas, particulate exposure, cardiopulmonary effects, Acute health effects, inhaled, cardiovascular morbifity, cardiopulmonary, cardiotoxicity, concentrated particulate matter, acute exposure, airborne urban contaminants, cardiovascular disease, exposure assessmentProgress 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.