Grantee Research Project Results
2014 Progress Report: Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM2.5 from Multipollutant Atmospheres in the Great Lakes Region
EPA Grant Number: R834797C002Subproject: this is subproject number 002 , established and managed by the Center Director under grant R834797
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Health Effects Institute (2005 — 2010)
Center Director: Greenbaum, Daniel S.
Title: Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM2.5 from Multipollutant Atmospheres in the Great Lakes Region
Investigators: Harkema, Jack , Fink, Greg , Wagner, James
Institution: Michigan State University
EPA Project Officer: Chung, Serena
Project Period: December 1, 2010 through November 30, 2015 (Extended to December 31, 2016)
Project Period Covered by this Report: August 1, 2013 through July 31,2014
RFA: Clean Air Research Centers (2009) RFA Text | Recipients Lists
Research Category: Human Health , Air
Objective:
Progress Summary:
Future Activities:
Ongoing Analyses:
- Cardiotelemetry Data Analysis: Data analysis of heart rate variability (HRV) in rats exposed to the O3/PM2.5 mixture, 5 days/wk for 4 weeks (Dexter inhalation exposure study) will be completed this year. A comparison of responses to O3/PM2.5 in Dexter vs. Dearborn will be conducted for HRV, heart rate and blood pressure. Lastly, we will assess exposure-related arrhythmias and ECG abnormalities in rats fed ND vs HFrD and exposed to O3, PM2.5, and O3/PM2.5 (coexposure) in all studies. These data will form the basis of two manuscripts.
- Associations of Exposure/Health Outcomes: Working in close collaboration with colleagues in the Exposure Core and the Biostatistics and Data Management Core, we will continue the correlation analyses to determine associations between acute cardiovascular responses (e.g., heart rate, mean arterial pressure, heart rate variability) and PM2.5 metrics (e.g., trace elements, gases, sources). We will conduct these correlative analyses to determine modifications by ozone coexposure on the source-induced cardiovascular health effects. These data will form the basis for at least one manuscript.
- Morphometric, Biochemical, and Molecular Analyses: We will complete these analyses of tissue (nose, lung, liver) and fluid (BALF and serum/plasma) samples taken from C57BL/6, KKAy, KK, RAG2(-/-) x γc(-/-) and RAG2(-/-) mice in our ongoing O3/PM2.5 studies. In addition, we will complete similar analyses taken from Sprague-Dawley rats in our collaborative study with colleagues in the Harvard CLARC (see below).
Short-term Studies:
- Study to identify the type of lymphoid cells responsible for the development of O3-induced eosinophilic rhinitis. We have demonstrated that lymphoid cells play a crucial role in the development of eosinophilic rhinitis in mice exposed to O3, but the type of lymphocytes involved is yet unknown. Based on our previous data and recently published articles in the scientific literature, we hypothesize that innate lymphoid cells (e.g., innate lymphoid 2 cells) are the primary effector cells. RAG2(-/-) mice (T and B lymphocyte deficient, but innate lymphoid cell sufficient) and RAG2(-/-) x γc(-/-) mice (deficient of all lymphoid cell types) will be exposed to O3 for 9 consecutive weekdays. If innate lymphoid cells do play a role in the development of O3-induced eosinophilic rhinitis, we anticipate that eosinophilic rhinitis will be induced in O3-exposed Rag 2(-/-) mice, but not in O3-exposed RAG2(-/-) x γc(-/-) mice.
- Study the role of insulin resistance in the enhanced sensitivity of diabetes-prone KKAy mice to O3-induced nasal and lung toxicity. Metformin is the most commonly prescribed drug for the treatment of type 2 diabetes, and the only anti-diabetic therapy that has been demonstrated to attenuate the cardiovascular complications of diabetes and metabolic syndrome. It also helps to reduce LDL cholesterol and triglyceride levels in the blood and improves insulin sensitivity. We will conduct a short-term inhalation study designed to determine if Metformin will protect diabetes-prone and hyperglycemic KKAy mice from O3-induced insulin resistance and O3-induced rhinitis and pneumonitis.
- Study to assess autonomic changes in rats exposed to ozone or PM2.5 by microneurographic recording. We will measure direct sympathetic nerve activity in rats pre-exposed to ozone or PM2.5. In these studies we will administer sympathomimetic and vasoactive agents to determine the association of changes in sympathetic activity with blood pressure in exposed versus nonexposed rats, and in rats fed normal versus high fructose diets.
Journal Articles on this Report : 14 Displayed | Download in RIS Format
Other subproject views: | All 73 publications | 28 publications in selected types | All 28 journal articles |
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Other center views: | All 148 publications | 72 publications in selected types | All 72 journal articles |
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Balasubramanian P, Sirivelu MP, Weiss KA, Wagner JG, Harkema JR, Morishita M, Mohankumar PS, Mohankumar SM. Differential effects of inhalation exposure to PM 2.5 on hypothalamic monoamines and corticotrophin releasing hormone in lean and obese rats. NeuroToxicology 2013;36:106-111. |
R834797 (2013) R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C002 (2012) R834797C002 (2013) R834797C002 (2014) R834797C002 (2015) R834797C002 (Final) |
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Brook RD, Bard RL, Kaplan MJ, Yalavarthi S, Morishita M, Dvonch JT, Wang L, Yang H-Y, Spino C, Mukherjee B, Oral EA, Sun Q, Brook JR, Harkema J, Rajagopalan S. The effect of acute exposure to coarse particulate matter air pollution in a rural location on circulating endothelial progenitor cells: results from a randomized controlled study. Inhalation Toxicology 2013;25(10):587-592. |
R834797 (2013) R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C001 (2013) R834797C001 (2014) R834797C001 (2015) R834797C001 (2016) R834797C001 (Final) R834797C002 (2013) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R834797C002 (Final) R834797C003 (2013) R834797C003 (Final) R833740 (2012) R833740 (Final) |
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Brook RD, Xu X, Bard RL, Dvonch JT, Morishita M, Kaciroti N, Sun Q, Harkema J, Rajagopalan S. Reduced metabolic insulin sensitivity following sub-acute exposures to low levels of ambient fine particulate matter air pollution. The Science of the Total Environment 2013;448:66-71. |
R834797 (2012) R834797 (2013) R834797 (2014) R834797 (2015) R834797 (Final) R834797C001 (2012) R834797C001 (2013) R834797C001 (2014) R834797C001 (2015) R834797C001 (2016) R834797C001 (Final) R834797C002 (2012) R834797C002 (2013) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R834797C002 (Final) R834797C003 (Final) |
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Brook RD, Bard RL, Morishita M, Dvonch JT, Wang L, Yang HY, Spino C, Mukherjee B, Kaplan MJ, Yalavarthi S, Oral EA, Ajluni N, Sun Q, Brook JR, Harkema J, Rajagopalan S. Hemodynamic, autonomic, and vascular effects of exposure to coarse particulate matter air pollution from a rural location. Environmental Health Perspectives 2014;122(6):624-630. |
R834797 (2013) R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C001 (2013) R834797C001 (2014) R834797C001 (2015) R834797C001 (2016) R834797C001 (Final) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R834797C002 (Final) R833740 (2012) R833740 (Final) |
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Liu C, Ying Z, Harkema J, Sun Q, Rajagopalan S. Epidemiological and experimental links between air pollution and type 2 diabetes. Toxicologic Pathology 2013;41(2):361-373. |
R834797 (2013) R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C002 (2012) R834797C002 (2013) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R834797C002 (Final) R834797C003 (2013) R834797C003 (2014) R834797C003 (2015) R834797C003 (Final) |
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Liu C, Xu X, Bai Y, Wang TY, Rao X, Wang A, Sun L, Ying Z, Gushchina L, Maiseyeu A, Morishita M, Sun Q, Harkema JR, Rajagopalan S. Air pollution-mediated susceptibility to inflammation and insulin resistance:influence of CCR2 pathways in mice. Environmental Health Perspectives 2014;122(1):17-26. |
R834797 (2013) R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R834797C002 (Final) R834797C003 (2014) R834797C003 (2015) R834797C003 (Final) |
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Liu C, Bai Y, Xu X, Sun L, Wang A, Wang TY, Maurya SK, Periasamy M, Morishita M, Harkema J, Ying Z, Sun Q, Rajagopalan S. Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus. Particle and Fibre Toxicology 2014;11:27. |
R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R834797C002 (Final) R834797C003 (2014) R834797C003 (2015) R834797C003 (Final) |
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Maiseyeu A, Yang H-Y, Ramanathan G, Yin F, Bard RL, Morishita M, Dvonch JT, Wang L, Spino C, Mukherjee B, Badgeley MA, Barajas-Espinosa A, Sun Q, Harkema J, Rajagopalan S, Araujo JA, Brook RD. No effect of acute exposure to coarse particulate matter air pollution in a rural location on high-density lipoprotein function. Inhalation Toxicology 2014;26(1):23-29. |
R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C001 (2014) R834797C001 (2015) R834797C001 (2016) R834797C001 (Final) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R833740 (Final) |
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Morishita M, Bard RL, Kaciroti N, Fitzner CA, Dvonch T, Harkema JR, Rajagopalan S, Brook RD. Exploration of the composition and sources of urban fine particulate matter associated with same-day cardiovascular health effects in Dearborn, Michigan. Journal of Exposure Science & Environmental Epidemiology 2015;25(2):145-152. |
R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C001 (2014) R834797C001 (2015) R834797C001 (2016) R834797C001 (Final) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R834797C002 (Final) R834797C003 (2015) R834797C003 (Final) |
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Ong CB, Kumagai K, Brooks PT, Brandenberger C, Lewandowski RP, Jackson-Humbles DN, Nault R, Zacharewski TR, Wagner JG, Harkema JR. Ozone-induced type 2 immunity in nasal airways. Development and lymphoid cell dependence in mice. American Journal of Respiratory Cell and Molecular Biology 2016;54(3):331-340. |
R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R834797C002 (Final) |
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Sun L, Liu C, Xu X, Ying Z, Maiseyeu A, Wang A, Allen K, Lewandowski RP, Bramble LA, Morishita M, Wagner JG, Dvonch JT, Sun Z, Yan X, Brook RD, Rajagopalan S, Harkema JR, Sun Q, Fan Z. Ambient fine particulate matter and ozone exposures induce inflammation in epicardial and perirenal adipose tissues in rats fed a high fructose diet. Particle and Fibre Toxicology 2013;10:43. |
R834797 (2013) R834797 (2014) R834797 (2015) R834797 (Final) R834797C001 (2013) R834797C002 (2013) R834797C002 (2014) R834797C002 (2015) R834797C002 (Final) R834797C003 (2013) R834797C003 (2014) R834797C003 (Final) |
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Wagner JG, Allen K, Yang HY, Nan B, Morishita M, Mukherjee B, Dvonch JT, Spino C, Fink GD, Rajagopalan S, Sun Q, Brook RD, Harkema JR. Cardiovascular depression in rats exposed to inhaled particulate matter and ozone: effects of diet-induced metabolic syndrome. Environmental Health Perspectives 2014;122(1):27-33. |
R834797 (2013) R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C001 (2013) R834797C001 (Final) R834797C002 (2013) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R834797C002 (Final) R834797C003 (2013) R834797C003 (Final) |
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Wagner JG, Kamal AS, Morishita M, Dvonch JT, Harkema JR, Rohr AC. PM2.5-induced cardiovascular dysregulation in rats is associated with elemental carbon and temperature-resolved carbon subfractions. Particle and Fibre Toxicology 2014;11:25 (10 pp.). |
R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R834797C002 (Final) |
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Ying Z, Xu X, Bai Y, Zhong J, Chen M, Liang Y, Zhao J, Liu D, Morishita M, Sun Q, Spino C, Brook RD, Harkema JR, Rajagopalan S. Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of sympathetic nervous system:a role for hypothalamic inflammation. Environmental Health Perspectives 2014;122(1):79-86. |
R834797 (2013) R834797 (2014) R834797 (2015) R834797 (2016) R834797 (Final) R834797C002 (2013) R834797C002 (2014) R834797C002 (2015) R834797C002 (2016) R834797C002 (Final) R834797C003 (2013) R834797C003 (2014) R834797C003 (2015) R834797C003 (Final) |
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Supplemental Keywords:
Relevant Websites:
Great Lakes Air Center For Integrated Environmental Research Exit
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R834797 Health Effects Institute (2005 — 2010) Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834797C001 Cardiometabolic Effects of Exposure to Differing Mixtures and Concentrations of PM2.5 in Obese and Lean Adults
R834797C002 Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM2.5 from Multipollutant Atmospheres in the Great Lakes Region
R834797C003 Long Term Metabolic Consequences of Exposures to Multipollutant Atmospheres in the Great Lakes Region
The 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.
Project Research Results
- Final Report
- 2016 Progress Report
- 2015 Progress Report
- 2013 Progress Report
- 2012 Progress Report
- 2011 Progress Report
- Original Abstract
28 journal articles for this subproject
Main Center: R834797
148 publications for this center
72 journal articles for this center