Grantee Research Project Results
Final Report: Long Term Health Effects of Concentrated Ambient PM2.5
EPA Grant Number: R827351C013Subproject: this is subproject number 013 , established and managed by the Center Director under grant R827351
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Health Effects Institute (2000 — 2005)
Center Director: Greenbaum, Daniel S.
Title: Long Term Health Effects of Concentrated Ambient PM2.5
Investigators: Chen, Lung Chi , Lippmann, Morton
Institution: New York University School of Medicine
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
Objective:
Both epidemiological studies and controlled laboratory studies in human subjects and animals have provided initial evidence that exposures to particulate matter (PM) pollution can have systemic, especially cardiovascular, effects. A very recent study on the largest cohort studied to date demonstrated that long-term exposure to PM2.5 is associated with increased risk of death from cardiopulmonary diseases via mechanisms involving inflammation, accelerated atherosclerosis, and altered cardiac autonomic function. Based on this background information, we conducted the first practical experimental system to study the acute and cumulative effects of daily inhalation exposures to inertially concentrated ambient-air particles (CAPs) at New York University’s (NYU) Sterling Forest, NY laboratory in a mouse model of atherosclerosis.
The objectives of this study were to:
- Determine the effects of subchronic CAPs exposure on pulmonary histopathology and lavage fluid biomarkers of lung inflammation and lung injury.
- Determine whether subchronic CAPs exposure accelerates the development of atherosclerotic plaques in a mouse model of human atherosclerotic cardiovascular disease (apoE-/- LDLr-/- mice).
Summary/Accomplishments (Outputs/Outcomes):
The results of the first of these studies, involving 5 to 6 months of warm-season daily exposures, indicated that subchronic CAPs exposure produced acute and chronic effects on cardiac function, increased amounts of and more invasive aortic plaque, and changes in brain cell distribution and in gene expression markers, as well as data on the effects of daily CAPs exposures in vitro on NfkB activation. Subsequently, using a senescent mouse model in a 3 month winter study, we were able to demonstrate that the CAPs exposures caused premature mortality, and that those mice with poorer cardiac function before the exposures became sicker and/or died sooner than those with better pre-exposure cardiac function. These findings support the need for targeted studies that help delineate the precise constituents in PM that confer health risk from particle air pollution and the molecular pathways involved, and provide a fundamental basis leading to the study in human population.
In this 3rd study, we showed that the relatively low CAPs concentration (av. = 85 μg/m3) imposed oxidative stress in the vasculature, altered vasomotor tone, induced vascular inflammation, and potentiated the development of atherosclerosis. We found that the results obtained using the UBM were similar to those by histopathology, verifying that the UBM is a valuable tool for periodic noninvasive monitoring of the progression of atherosclerosis. In addition, there was marked infiltration of macrophages in the aortic plaques, and some evidence that increased tissue factor gene expression in plaque and smooth muscle may be responsible for the exacerbation of atherosclerosis by subchronic CAPs exposure. Our findings provide a biologic basis for the association between atherosclerosis related events noted in time series analysis and prospective population cohort studies, suggesting that even seemingly low concentrations of PM2.5 exposure, may have important detrimental effects on the vasculature.
Conclusions:
Subchronic exposure of CAPs (average concentration 110 μg/m3) produced changes in heart rate (HR) and heart rate variability (HRV); enhanced atherosclerotic plaques on endothelia; altered gene expressions in the lung and heart tissues; and altered brain cell distributions in ApoE-/- mice susceptible to atherosclerosis. We further found that the relatively low CAPs concentration (av. = 85 μg/m3) imposed oxidative stress in the vasculature, altered vasomotor tone, induced vascular inflammation, and potentiated the development of atherosclerosis. In addition, dramatic alterations in HR and HRV were found to be associated with a short-term peak Ni, Fe, and Cr concentrations while NF-κB activation appeared to be depending on V and Ni from regional sources.
Technical Report:
Long Version of Final Report (PDF) (12 pp, 322 K, About PDF)
Journal Articles on this Report : 11 Displayed | Download in RIS Format
Other subproject views: | All 11 publications | 11 publications in selected types | All 11 journal articles |
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Other center views: | All 112 publications | 101 publications in selected types | All 89 journal articles |
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Chen LC, Hwang JS. Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice. IV. Characterization of acute and chronic effects of ambient air fine particulate matter exposures on heart-rate variability. Inhalation Toxicology 2005;17(4-5):209-216. |
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Chen LC, Nadziejko C. Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice: V. CAPs exacerbate aortic plaque development in hyperlipidemic mice. Inhalation Toxicology 2005;17(4-5):217-224. |
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Gunnison A, Chen LC. Effects of subchronic exposures to concentrated ambient particles in mice: VI. Gene expression in heart and lung tissue. Inhalation Toxicology 2005;17(4-5):225-233. |
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Hwang J-S, Nadziejko C, Chen LC. Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice: III. Acute and chronic effects of CAPs on heart rate, heart-rate fluctuation, and body temperature. Inhalation Toxicology 2005;17(4-5):199-207. |
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Lippmann M, Gordon T, Chen LC. Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice: I. Introduction, objectives, and experimental plan. Inhalation Toxicology 2005;17(4-5):177-187. |
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Lippmann M, Gordon T, Chen LC. Effects of subchronic exposures to concentrated ambient particles in mice: IX. Integral assessment and human health implications of subchronic exposures of mice to CAPs. Inhalation Toxicology 2005;17(4-5):255-261. |
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Lippmann M, Hwang JS, Maciejczyk P, Chen LC. PM source apportionment for short-term cardiac function changes in ApoE-/- mice. Environmental Health Perspectives 2005;113(11):1575-1579. |
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Maciejczyk P, Zhong MH, Li Q, Xiong J, Nadziejko C, Chen LC. Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice: II. The design of a CAPs exposure system for biometric telemetry monitoring. Inhalation Toxicology 2005;17(4-5):189-197. |
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Maciejczyk P, Chen LC. Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice: VIII. Source-related daily variations in in vitro responses to CAPs. Inhalation Toxicology 2005;17(4-5):243-253. |
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Sun Q, Wang A, Jin X, Natanzon A, Duquaine D, Brook RD, Aquinaldo JG, Fayad ZA, Fuster V, Lippmann M, Chen LC, Rajagopalan S. Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. JAMA-Journal of the American Medical Association 2005;294(23):3003-3010. |
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Veronesi B, Makwana O, Pooler M, Chen LC. Effects of subchronic exposure to concentrated ambient particles: VII. Degeneration of dopaminergic neurons in Apo E-/-mice. Inhalation Toxicology 2005;17(4-5):235-241. |
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Supplemental Keywords:
subchronic, source apportionment, oxidative stress, PM component,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, ENVIRONMENTAL MANAGEMENT, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Environmental Monitoring, Physical Processes, Risk Assessment, ambient air quality, atmospheric particulate matter, particulates, air toxics, atmospheric particles, chemical characteristics, toxicology, ambient air monitoring, acute lung injury, PM 2.5, long term exposure, airborne particulate matter, environmental risks, exposure, epidemelogy, air pollution, aerosol composition, atmospheric aerosol particles, human exposure, PM, exposure assessmentRelevant Websites:
Long Version of Final Report (PDF) (12 pp, 322 K, About PDF)
http://www.med.nyu.edu/environmental/ Exit
https://www.epa.gov/research-grants/
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R827351 Health Effects Institute (2000 — 2005) Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827351C001 Exposure Characterization Error
R827351C002 X-ray CT-based Assessment of Variations in Human Airway Geometry: Implications for Evaluation of Particle Deposition and Dose to Different Populations
R827351C003 Asthma Susceptibility to PM2.5
R827351C004 Health Effects of Ambient Air PM in Controlled Human Exposures
R827351C005 Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity
R827351C006 Effects of Particle-Associated Irritants on the Cardiovascular System
R827351C007 Role of PM-Associated Transition Metals in Exacerbating Infectious Pneumoniae in Exposed Rats
R827351C008 Immunomodulation by PM: Role of Metal Composition and Pulmonary Phagocyte Iron Status
R827351C009 Health Risks of Particulate Matter Components: Center Service Core
R827351C010 Lung Hypoxia as Potential Mechanisms for PM-Induced Health Effects
R827351C011 Urban PM2.5 Surface Chemistry and Interactions with Bronchoalveolar Lavage Fluid (BALF)
R827351C012 Subchronic PM2.5 Exposure Study at the NYU PM Center
R827351C013 Long Term Health Effects of Concentrated Ambient PM2.5
R827351C014 PM Components and NYC Respiratory and Cardiovascular Morbidity
R827351C015 Development of a Real-Time Monitoring System for Acidity and Soluble Components in Airborne Particulate Matter
R827351C016 Automated Real-Time Ambient Fine PM Monitoring System
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
11 journal articles for this subproject
Main Center: R827351
112 publications for this center
89 journal articles for this center