It has been well documented that exposure to fine ambient air particulate matter (PM2.5) induces consistent increased risk for cardiovascular disorders (CVD) in humans at the levels currently encountered in the U.S. However, the mechanism(s) and component(s) responsible for PM2.5 associated cardiovascular effects are still unknown. In our recent subchronic inhalation study, we observed that dramatic increases in heart rate and decreases in heart rate variability occurred in the ApoE-/- mouse model on days when PM2.5 contained elevated concentrations of nickel (Ni) as compared to days with typically lower Ni exposure. We further found in humans that Ni and vanadium best explained the variation of the NMMAPS PM10 mortality risk coefficients across cities. Therefore, we hypothesize that Ni is a major component responsible for PM2.5 associated CVD. It has been difficult, however, to test this hypothesis due to lack of appropriate populations with adequate combination of exposures to both PM2.5 and Ni in the U.S. Recently, we identified two large cities in China, which have exposures to similar ambient PM2.5 mass concentrations but very different levels of Ni (~500ng Ni/m3 in Jinchang and ~10 ng Ni/m3 in Zhanye). Therefore, we propose to evaluate the feasibility of using these ideal and unique populations to examine the potential roles of Ni in PM2.5 associated CVD through population- based mortality and morbidity and panel-based biomarker studies.
The specific aims of the study are: 1) to examine the feasibility of conducting time-series analyses of CVD mortality and morbidity in the overall populations of the two Chinese cites to identify the potential mechanistic roles of Ni in PM2.5 associated CVD;2) to determine whether or not the commonly used CVD biomarkers can be employed to evaluate the role of Ni in PM2.5 related CVD in the identified populations. The candidate biomarkers of CVD include proinflammatory markers [IL-6, and C reactive protein (CRP)];markers of leukocyte recruitment [monocyte chemoattractant protein 1 (MCP-1)];and endothelial dysfunction biomarkers (ICAM and VCAM). This study will provide insights into the role of, and mechanism for action of a highly likely PM2.5 component in terms of inducing CVD. This study should have significant implications for both research and legislative regulation in controlling the health hazards associated with ambient PM exposure.

Public Health Relevance

Particulate matter (PM) in ambient air is a mixture and a ubiquitous pollutant that induces consistent increase in hospital admission and death of cardiovascular disorders (CVD) in humans at the levels currently encountered in the U.S. However, why PM causes CVD is still unknown. This study was proposed to address the role that nickel may play in PM associated CVD. The study is relevant to the major environmental health issues and should have significant implications for both research and legislative regulation in controlling the health hazards associated with ambient PM exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21ES016570-02
Application #
7752609
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Dilworth, Caroline H
Project Start
2009-01-01
Project End
2011-12-31
Budget Start
2010-01-01
Budget End
2011-12-31
Support Year
2
Fiscal Year
2010
Total Cost
$183,150
Indirect Cost
Name
New York University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Liberda, Eric N; Cuevas, Azita K; Qu, Qingshan et al. (2014) The acute exposure effects of inhaled nickel nanoparticles on murine endothelial progenitor cells. Inhal Toxicol 26:588-97
Niu, Jingping; Liberda, Eric N; Qu, Song et al. (2013) The role of metal components in the cardiovascular effects of PM2.5. PLoS One 8:e83782
Liberda, Eric N; Cuevas, Azita K; Gillespie, Patricia A et al. (2010) Exposure to inhaled nickel nanoparticles causes a reduction in number and function of bone marrow endothelial progenitor cells. Inhal Toxicol 22 Suppl 2:95-9
Qu, Song; Liberda, Eric N; Qu, Qingshan et al. (2010) In vitro assessment of the inflammatory response of respiratory endothelial cells exposed to particulate matter. J Toxicol Environ Health A 73:1113-21
Wang, Shang; Prophete, Colette; Soukup, Joleen M et al. (2010) Roles of MAPK pathway activation during cytokine induction in BEAS-2B cells exposed to fine World Trade Center (WTC) dust. J Immunotoxicol 7:298-307