Air Pollution and Human Vascular Dysfunction: Mechanism and MediatorsEPA Grant Number: CR830837
Title: Air Pollution and Human Vascular Dysfunction: Mechanism and Mediators
Investigators: Brook, Robert D. , Brook, Jeffrey R. , Dvonch, Joseph T. , Keeler, Gerald J. , Rajagopalan, Sanjay , Silverman, Frances , Vincent, Renaud
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 Amount: $1,050,000
RFA: Airborne Particulate Matter Health Effects: Cardiovascular Mechanisms (2002) RFA Text | Recipients Lists
Research Category: Health Effects , Particulate Matter , Air
Short-term exposure to concentrated ambient fine particulate air pollution (PM2.5) + ozone (O3) causes acute conduit artery vasoconstriction. 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.
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.
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.