Traffic related air pollution has been associated with exacerbation of heart disease, specifically, it triggers hospital admissions for heart attacks, irregular heart rhythms, episodes of heart failure and deaths from heart disease. Diesel exhaust particles (DEP) is an important component of urban traffic related air pollutants. The overall objective of this study is to determine the effects of DEP exposure on blood vessels. Our broad hypothesize is that air pollutants impact blood vessels resulting in adverse cardiovascular health effects. We propose to use as well established model of DEP exposure of older Apo-E knock-out mice, mice that naturally develop atherosclerosis, the underlying disease resulting in heart attacks and stroke. This model represents subjects at risk for the adverse effects of air pollution as shown in epidemiological studies, namely older subjects with pre-existing atherosclerosis. We will pursue the following specific aims: 1) Functional studies on the responses of blood vessels following DEP exposure. These studies involved harvesting the aorta from mice exposed to DEP for 7 weeks and expose these vessels to different agonist and antagonist, measuring the ability of vessels to constrict and dilate. 2) Determine the different pathways activated in the endothelium of blood vessels that could be involved in the abnormal functional response of blood vessels following DEP exposure. 3) Measurement of circulating pro-inflammatory mediators that in include acute phase proteins, cytokines and leukocytes as well as vasoactive mediators such as Nitric Oxide and endothelins that has been implicated in abnormal vascular responses following air pollution exposure. 4) Quantitative histological studies to quantify the lung inflammation induced by DEP exposure as well as the particle burden in the lung and relate these to the downstream abnormal vascular response of blood vessels. Numerous epidemiological studies have implicated exposure to air pollution particles to adverse effects on the heart and blood vessels. The mechanisms how inhalation of particles into the lung impact blood vessels, are unclear and is the focus of this proposal. This research will advance our insights in how deposition of fine particles in the lung results in adverse health effects such as triggering angina, a heart attack or stroke. Understanding these mechanisms could help to determine what potential therapeutic intervention could prevent the adverse health effects of air pollutants on the heart and blood vessels.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Specialized Center (P50)
Project #
5P50ES015915-05
Application #
8376274
Study Section
Special Emphasis Panel (ZES1-JAB-C)
Project Start
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
5
Fiscal Year
2012
Total Cost
$307,432
Indirect Cost
$99,271
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Bell, Griffith; Mora, Samia; Greenland, Philip et al. (2017) Association of Air Pollution Exposures With High-Density Lipoprotein Cholesterol and Particle Number: The Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol 37:976-982
Gepner, Adam D; Tedla, Yacob; Colangelo, Laura A et al. (2017) Progression of Carotid Arterial Stiffness With Treatment of Hypertension Over 10 Years: The Multi-Ethnic Study of Atherosclerosis. Hypertension 69:87-95
Sack, Coralynn; Vedal, Sverre; Sheppard, Lianne et al. (2017) Air pollution and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA) air-lung study. Eur Respir J 50:
Tedla, Yacob G; Yano, Yuichiro; Carnethon, Mercedes et al. (2017) Association Between Long-Term Blood Pressure Variability and 10-Year Progression in Arterial Stiffness: The Multiethnic Study of Atherosclerosis. Hypertension 69:118-127
Gepner, Adam D; Young, Rebekah; Delaney, Joseph A et al. (2017) Comparison of Carotid Plaque Score and Coronary Artery Calcium Score for Predicting Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc 6:
Yoneyama, S; Yao, J; Guo, X et al. (2017) Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations. Int J Obes (Lond) 41:324-331
Sack, Cora S; Kaufman, Joel D (2016) Air Pollution Levels and Children's Lung Health. How Low Do We Need to Go? Am J Respir Crit Care Med 193:819-20
Bergen, Silas; Sheppard, Lianne; Kaufman, Joel D et al. (2016) Multipollutant measurement error in air pollution epidemiology studies arising from predicting exposures with penalized regression splines. J R Stat Soc Ser C Appl Stat 65:731-753
Chi, Gloria C; Liu, Yongmei; MacDonald, James W et al. (2016) Long-term outdoor air pollution and DNA methylation in circulating monocytes: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Environ Health 15:119
Spalt, Elizabeth W; Curl, Cynthia L; Allen, Ryan W et al. (2016) Time-location patterns of a diverse population of older adults: the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). J Expo Sci Environ Epidemiol 26:349-55

Showing the most recent 10 out of 80 publications