The overall objective of this DISCOVER Center is to investigate the mechanisms by which traffic-related air pollution causes myocardial infarction and other cardiovascular diseases, by integrating a diverse set of research approaches. Air pollution exposures have been consistently associated with cardiovascular disease. A growing literature indicates that the major source of variation in air pollution's cardiovascular health effects is from exposure to traffic. Diesel exhaust is an excellent model exposure. The closely linked suite of activities in this DISCOVER Center will attempt to understand the mechanisms (molecular mechanisms that cause vasoconstriction and acceleration of atherosclerosis) underlying exposure-related effects, and use environmental exposures to understand basic mechanisms regarding vascular biology. The studies will exploit exposure contrasts in experimental and epidemiological studies through advanced exposure assessment methods, and genetic diversity in both human and animal studies, to advance our aims. The application brings together a cohesive group of five projects (two patient-oriented and three basic mechanistic studies) and three cores, Administrative, Exposure Science, and Biostatistics and Bioinformatics. Project 1 investigates the mechanism underlying vascular response in humans following controlled exposure to diesel exhaust;Project 2 studies genetic modifiers on the effect of traffic-related air pollution on vascular response and atherosclerosis in a population-based human observational study. Project 3 investigates the role of systemic inflammation in the vascular response to diesel exhaust. Project 4 investigates the impact of diesel exhaust exposure on myocardial injury and apoptosis. Project 5 investigates reactive oxygen species and oxidative stress in the vascular response to diesel exhaust. Through this research, the investigators will develop knowledge that can be used to develop preventive and therapeutic strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Specialized Center (P50)
Project #
5P50ES015915-05
Application #
8278537
Study Section
Special Emphasis Panel (ZES1-JAB-C (DI))
Program Officer
Mcallister, Kimberly A
Project Start
2008-06-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2012
Total Cost
$2,402,615
Indirect Cost
$873,368
Name
University of Washington
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Stern, Rebecca; Tattersall, Matthew C; Gepner, Adam D et al. (2015) Sex differences in predictors of longitudinal changes in carotid artery stiffness: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol 35:478-84
Kim, Sun-Young; Sheppard, Lianne; Kaufman, Joel D et al. (2014) Individual-level concentrations of fine particulate matter chemical components and subclinical atherosclerosis: a cross-sectional analysis based on 2 advanced exposure prediction models in the multi-ethnic study of atherosclerosis. Am J Epidemiol 180:718-28
Gepner, Adam D; Korcarz, Claudia E; Colangelo, Laura A et al. (2014) Longitudinal effects of a decade of aging on carotid artery stiffness: the multiethnic study of atherosclerosis. Stroke 45:48-53
Tattersall, Matthew C; Gassett, Amanda; Korcarz, Claudia E et al. (2014) Predictors of carotid thickness and plaque progression during a decade: the Multi-Ethnic Study of Atherosclerosis. Stroke 45:3257-62
Gepner, Adam D; Colangelo, Laura A; Blondon, Marc et al. (2014) 25-hydroxyvitamin D and parathyroid hormone levels do not predict changes in carotid arterial stiffness: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol 34:1102-9
Weldy, Chad S; Liu, Yonggang; Liggitt, H Denny et al. (2014) In utero exposure to diesel exhaust air pollution promotes adverse intrauterine conditions, resulting in weight gain, altered blood pressure, and increased susceptibility to heart failure in adult mice. PLoS One 9:e88582
Szpiro, Adam A; Sheppard, Lianne; Adar, Sara D et al. (2014) Estimating acute air pollution health effects from cohort study data. Biometrics 70:164-74
Lindström, Johan; Szpiro, Adam A; Sampson, Paul D et al. (2014) A Flexible Spatio-Temporal Model for Air Pollution with Spatial and Spatio-Temporal Covariates. Environ Ecol Stat 21:411-433
Adar, Sara D; Sheppard, Lianne; Vedal, Sverre et al. (2013) Fine particulate air pollution and the progression of carotid intima-medial thickness: a prospective cohort study from the multi-ethnic study of atherosclerosis and air pollution. PLoS Med 10:e1001430
Krishnan, Ranjini M; Sullivan, Jeffrey H; Carlsten, Chris et al. (2013) A randomized cross-over study of inhalation of diesel exhaust, hematological indices, and endothelial markers in humans. Part Fibre Toxicol 10:7

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