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Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity
EPA Grant Number: R832416C001Subproject: this is subproject number 001 , established and managed by the Center Director under grant R832416
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Harvard Particle Center
Center Director: Koutrakis, Petros
Title: Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity
Investigators: Schwartz, Joel , Suh, Helen H. , Vokonas, Pantel
Current Investigators: Schwartz, Joel , Sparrow, David , Suh, Helen H. , Vokonas, Pantel
Institution: Harvard University , Boston University
Current Institution: Harvard School of Public Health
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: October 1, 2005 through September 30, 2010
RFA: Particulate Matter Research Centers (2004)
Research Category: Particulate Matter
Description:
Objective:Since 1997, epidemiological and animal studies have identified many potential mechanisms by which particles may impact health. However, the relative importance of these potential pathways and the steps along these pathways are not well understood, particularly as to how they relate to specific particle components and sources, for which pathways are likely to differ. We propose to examine the importance and relevance of the inflammatory, endothelial and autonomic pathways to particle toxicity using the cohort of individuals participating in the Normative Aging Study (NAS), a large prospective cohort living in Eastern Massachusetts.
Approach:We propose to build on our analyses of the NAS cohort performed as part of our original EPA-Harvard Particle Health Effects Center using novel exposure and epidemiological approaches. This approach uses pharmacological and natural interventions as well as genetics, to highlight specific biological pathways. Specifically, we propose to collect ECG, blood inflammatory marker, medication, genotypic, food frequency, and particle exposure data for each of the 700 current NAS participants. ECG and blood marker samples will be analyzed for a variety of measures (HRV, ST segments, QT intervals, CRP, sICAM-1, sVCAM-1, and homocysteine) that will serve as intermediate markers of the inflammatory, endothelial, and autonomic pathways. These markers will be related to individual-specific PM2.5, SO42-, BC and trace element exposures that will be measured inside each participant's home for one-week prior to his/her clinic visit and to ambient air pollution (PM2.5, PM10, PM2.5-10, SO42 , NO3-, BC, EC, OC, NO3-, PC, and trace elements) concentrations that will be measured at our stationary ambient monitoring (SAM) site. The long-term (i.e., annual) effects of specific particle component exposures on measured markers of inflammation, endothelial function, and autonomic function will also be examined using a GIS-based exposure model. The importance and relevance of the inflammatory, endothelial and autonomic pathways of particle toxicity will be examined using naturally occurring variations in the NAS cohort in: (a) the GSTM1 and HO-1 genotypes; (b) dietary micronutrient intake; (c) hypertensive and cardiac medication use, and; (d) methacholine reactivity.
Expected Results:By examining how these variations modify exposure-effect relationships, natural interventions will be created that enhance or diminish the importance of the inflammatory, endothelial, and autonomic pathways. Given these variations, structural equation models, a powerful technique that combines multiple regression and factor analysis methods, will be used to examine relationships among the multiple PM components and health outcomes and to determine whether these relationships are consistent with specific biological pathways.
Supplemental Keywords:susceptible sub-populations, response heterogeneity, biological mechanism,
,
Air, Scientific Discipline, Health, RFA, Risk Assessments, Health Risk Assessment, Epidemiology, particulate matter, Environmental Chemistry, ambient air quality, cardiovascular vulnerability, chemical characteristics, autonomic dysfunction, traffic related particulate matter, chemical composition, human health risk, oxidative stress, human health effects, toxicology, automobile exhaust, ambient particle health effects, atmospheric particulate matter, biological mechanism , airborne particulate matter, human exposure, biological mechanisms
Progress and Final Reports:
2006 Progress Report
2007 Progress Report
Main Center Abstract and Reports:
R832416 Harvard Particle Center
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832416C001 Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity
R832416C002 Cardiovascular Toxicity of Concentrated Ambient Fine, Ultrafine and Coarse Particles in Controlled Human Exposures
R832416C003 Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs
R832416C004 Cardiovascular Effects of Mobile Source Exposures: Effects of Particles and Gaseous Co-pollutants
R832416C005 Toxicological Evaluation of Realistic Emission Source Aerosol (TERESA): Investigation of Vehicular Emissions