Grantee Research Project Results
2006 Progress Report: Air Pollution and Human Vascular Dysfunction: Mechanism and Mediators
EPA Grant Number: CR830837Title: Air Pollution and Human Vascular Dysfunction: Mechanism and Mediators
Investigators: Brook, Robert D. , Keeler, Gerald J. , Brook, Jeffrey R. , Dvonch, Joseph T. , Silverman, Frances , Vincent, Renaud , Rajagopalan, Sanjay
Institution: University of Michigan , University of Toronto
Current Institution: University of Michigan , Health Canada - Ottawa , University of Toronto
EPA Project Officer: Chung, Serena
Project Period: May 1, 2003 through April 30, 2006 (Extended to April 30, 2008)
Project Period Covered by this Report: May 1, 2006 through April 30,2007
Project Amount: $1,050,000
RFA: Airborne Particulate Matter Health Effects: Cardiovascular Mechanisms (2002) RFA Text | Recipients Lists
Research Category: Human Health , Particulate Matter , Air
Objective:
Short-term exposure to concentrated ambient fine particulate air pollution (PM2.5) + ozone (O3) causes acute conduit artery vasoconstriction and increases the risk for acute myocardial infarction. This abrupt alteration in vascular tone is likely an important biological mechanism linking air pollution exposure with acute cardiovascular events. The objectives of this current proposal are threefold. First, to elucidate the underlying patho-physiological mechanisms linking air pollution with impaired arterial reactivity; second, to determine the significance of the air pollution-mediated arterial vasoconstriction on systemic hemodynamics and blood pressure; and third, to identify the specific air pollution components responsible for the detrimental impact on human vascular function.
Approach:
We plan to undertake two separate double-blind, cross-over studies using controlled human exposures to concentrated ambient PM2.5 (CAP) ± O3. A new mobile human exposure facility (AirCARE 1) will be employed at the University of Michigan to focus on the underlying biological mechanisms. AirCARE 1 is the result of a joint collaboration between the University of Michigan and Michigan State University. The effects of pre-exposure treatments with anti-oxidants and endothelin receptor blockade on the vascular responses to air pollution exposure will be investigated compared to placebo. The exposure facility located at the University of Toronto will be used to investigate the importance of CAP versus O, as well as specific particle constituents, in the etiology of the vascular dysfunction following air pollution exposure.
Progress Summary:
This research study is divided into 2 projects. Project 1 has been investigating the mechanisms of acute vascular dysfunction related to exposure to CAP and ozone. In particular, the roles played by oxidative stress (impact of vitamin C pre-treatment) and endothelins (effect of bosentan pre-treatment) are being evaluated vs the effect of placebo pre-treatment. As of June 2007 project 1 has been completed. We enrolled 50 subjects with 3 exposures each (150 exposures in total). Specific outcomes regarding vascular endothelial function, 24 hour blood pressure, platelet aggregation, inflammatory bio-markers, and arterial compliance have been collected and will be analyzed by the end of 2007. Project 2 is investigating the specific air pollutant mediators of adverse cardiovascular responses. As of June 2007 project 2 has completed 34 subjects. We will enroll 38 subjects, each exposed to CAP, filtered air, CAP + ozone, and ozone alone (4 exposures each) by the end of 2007. This is a total of 152 exposures.
Expected Results:
It is anticipated that CAP (PM2.5) will be primarily implicated in mediating the adverse effects on the vasculature and that both pre-exposure treatments with anti-oxidants and ET-blockade will prevent or significantly blunt the air pollution-mediated vasoconstriction. The results of this study will provide important insights into the biological mechanism linking air pollution with cardiovascular disease, supporting a crucial role of oxidative stress and heightened vascular expression of ETs.
Future Activities:
Projects 1 and 2 are now complete. Data are planned to be analyzed and results presented in 2007.
Journal Articles:
No journal articles submitted with this report: View all 5 publications for this projectSupplemental Keywords:
concentrated ambient air, ozone, health effects, endothelium, atherosclerosis, concentrated ambient air pollution,, RFA, Scientific Discipline, Health, Air, particulate matter, Health Risk Assessment, Risk Assessments, Biochemistry, atmospheric particulate matter, particulates, human health effects, PM 2.5, airway disease, ozone, airborne particulate matter, cardiovascular vulnerability, air pollution, human exposure, vascular dysfunction, cardiovascular diseaseRelevant Websites:
http://www.med.umich.edu/endothelial/index.htm Exit
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.