Air pollution is positively associated with an increased daily incidence of myocardial infarction and cardiovascular mortality. Recent findings strongly implicate a role for fresh vehicular exhaust, clearly showing elevated coronary events related acutely to traffic exposure. Clinical and experimental research suggests that air pollutants can acutely induce a vasoconstrictive mechanism, though a clear connection between such studies and the ultimate cardiac sequelae has not been confirmed. The proposed study will seek to validate our previous observations that specific gaseous components of engine exhaust, which are a significant contributor to ambient air pollution, may have pathological vasoactive properties by blunting coronary dilation and enhancing constriction. ECG and vascular abnormalities in ApoE-/- mice occurred when exposed by inhalation to fresh diesel or gasoline exhaust, but not aged, resuspended road dust, suggest that certain compounds in fresh emissions that drive cardiovascular responses may be lost in collected or concentrated particles. Many volatile and semivolatile compounds in fresh emissions can exist in both the gaseous and particulate phases of whole exhaust, and it may be that attempts to ascertain toxicity of filter-collected or concentrated PM may underestimate the adverse health effects by eliminating the gaseous co-pollutants. We have three primary hypotheses to test in this study: (1) We hypothesize that gaseous components of whole emissions can exert effects directly on vascular tissue as well as indirectly by oxidatively modifying endogenous circulating phospholipids, thereby altering the native function of those lipids. Our findings of oxidized low density lipoprotein in the circulation and lipid peroxidation by-products in the vasculature of engine emission-exposed mice, in the absence of overt pulmonary or systemic inflammation suggests that there may be a mild oxidative process in the lung that transfers systemically;(2) We hypothesize that the predominant mechanism driving impaired dilatory function is the formation of peroxynitrite and uncoupling of endothelial nitric oxide synthase. Nitrotyrosine is upregulated in the vasculature following chronic, low-level gasoline exhaust exposure, but it is unknown to what degree peroxynitrite impacts acutely on the vessels;and (3) We hypothesize that observed T-wave abnormalities reflect emission-induced impairment of endothelial cell function, leading to diminished coronary flow and myocardial ischemia in vulnerable subjects. Findings of air pollution-induced rat and mouse ECG abnormalities from several laboratories have not been validated in terms of absolute cardiovascular pathology;we predict diminished coronary flow and mild ischemia will occur in the susceptible mouse strain (ApoE-/-).

Public Health Relevance

Cardiovascular effects of air pollution are becoming recognized as a major public health concern. These studies will examine both biological and chemical mechanisms of air pollution-induced adverse coronary events. Results from these studies will assist in the assessment and management of personal risk of health effects from air pollution exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES014639-06
Application #
8254448
Study Section
Myocardial Ischemia and Metabolism Study Section (MIM)
Program Officer
Nadadur, Srikanth
Project Start
2008-05-01
Project End
2013-09-24
Budget Start
2012-03-01
Budget End
2013-09-24
Support Year
6
Fiscal Year
2012
Total Cost
$329,277
Indirect Cost
$108,754
Name
University of New Mexico
Department
Other Health Professions
Type
Schools of Pharmacy
DUNS #
868853094
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Zychowski, Katherine E; Sanchez, Bethany; Pedrosa, Rodrigo P et al. (2016) Serum from obstructive sleep apnea patients induces inflammatory responses in coronary artery endothelial cells. Atherosclerosis 254:59-66
Aragon, Mario J; Chrobak, Izabela; Brower, Jeremy et al. (2016) Inflammatory and Vasoactive Effects of Serum Following Inhalation of Varied Complex Mixtures. Cardiovasc Toxicol 16:163-71
Mumaw, Christen L; Levesque, Shannon; McGraw, Constance et al. (2016) Microglial priming through the lung-brain axis: the role of air pollution-induced circulating factors. FASEB J 30:1880-91
Brower, Jeremy B; Doyle-Eisele, Melanie; Moeller, Benjamin et al. (2016) Metabolomic changes in murine serum following inhalation exposure to gasoline and diesel engine emissions. Inhal Toxicol 28:241-50
Harmon, Molly E; Campen, Matthew J; Miller, Curtis et al. (2016) Associations of Circulating Oxidized LDL and Conventional Biomarkers of Cardiovascular Disease in a Cross-Sectional Study of the Navajo Population. PLoS One 11:e0143102
Zychowski, Katherine E; Lucas, Selita N; Sanchez, Bethany et al. (2016) Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure. Toxicol Appl Pharmacol 305:40-5
Tyler, Christina R; Zychowski, Katherine E; Sanchez, Bethany N et al. (2016) Surface area-dependence of gas-particle interactions influences pulmonary and neuroinflammatory outcomes. Part Fibre Toxicol 13:64
Aragon, Mario; Erdely, Aaron; Bishop, Lindsey et al. (2016) MMP-9-Dependent Serum-Borne Bioactivity Caused by Multiwalled Carbon Nanotube Exposure Induces Vascular Dysfunction via the CD36 Scavenger Receptor. Toxicol Sci 150:488-98
Paffett, Michael L; Zychowski, Katherine E; Sheppard, Lianne et al. (2015) Ozone Inhalation Impairs Coronary Artery Dilation via Intracellular Oxidative Stress: Evidence for Serum-Borne Factors as Drivers of Systemic Toxicity. Toxicol Sci 146:244-53
Schisler, Jonathan C; Ronnebaum, Sarah M; Madden, Michael et al. (2015) Endothelial inflammatory transcriptional responses to an altered plasma exposome following inhalation of diesel emissions. Inhal Toxicol 27:272-80

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