Animal models: Cardiovascular Disease, CNS Injury and Ultrafine Particle Biokinetics

EPA Grant Number: R832415C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R832415
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Rochester PM Center
Center Director: Oberdörster, Günter
Title: Animal models: Cardiovascular Disease, CNS Injury and Ultrafine Particle Biokinetics
Investigators: Oberdörster, Günter , Couderc, Jean-Philippe , Elder, Alison C.P. , Gelein, Robert , Kreyling, Wolfgang , Oakes, David , Phipps, Richard
Institution: University of Rochester , GSF-National Research Center for Environment and Health
EPA Project Officer: Hunt, Sherri
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2012)
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

The animal studies are designed to test our central hypothesis that ambient ultrafine (UF) particles induce oxidative injury in target cells of the cardiovascular system, resulting in adverse health effects in susceptible parts of the population. The goals of the animal studies are to (i) Identify cellular mechanisms that lead to systemic and thrombogenic responses and associated cardiac events; (ii) Identify the particle sizes and chemical constituents that induce effects; (iii) Define pathways of direct UF/fine translocation to extrapulmonary sites; (iv) Evaluate the neurotoxic potential of UF/fine PM exposure; and (v) Analyze mechanistic pathways linking PM inhalation and deposition in the respiratory tract with effects at the portal of entry and in remote organs.

Approach:

The diabetic JCR rats will be used as a model of cardiovascular susceptibility to identify mechanisms of PM-induced thrombogenic events following acute and subchronic inhalation exposures to concentrated ambient UF/fine particles. Additional exposures of JCR rats to freshly-generated Diesel exhaust from a truck equipped with future (2007) filter trap technology will also be performed, using a mobile laboratory while driving on highways. Other animal studies will evaluate potential neurotoxic effects using a mouse model of neurodegeneration and subchronic exposures to ambient concentrated UF/fine particles. Particle size-dependent translocation pathways of inhaled UF/fine particles from the respiratory tract to extrapulmonary target tissues, including endothelial cells, blood platelets, bone marrow, heart, and CNS will also be examined. These studies are designed in close collaboration with the other Research Cores: information provided by the PM Characterization and Source Apportionment Research Core (Core 1) is an integral part of the animal studies, which are complementary to the epidemiological (Core 2) and controlled clinical studies (Core 3), and provide a link to the mechanistic in vitro studies (Core 5). In addition, this Core has strong collaborative ties to the Center's four Facility Cores: Biostatistics, Aerosol Generation and Analysis, Vascular and Inflammation, and Cardiac.

Expected Results:

The Animal Core studies will help to answer the question of why subpopulations are at increased risk of adverse health outcomes following PM exposure. They will identify the cellular and molecular mechanisms which underlie cardiovascular susceptibility. Exposure-response relationships will be defined and we expect to learn how exposure duration, temporal variability in PM concentration and composition affect responses. Results of the animal studies, integrated with those of the epidemiological, controlled clinical, and in vitro studies, along with source-specific PM characterization and source apportionment analyses, will be used for correlating effects with specific PM constituents and sources.

Publications and Presentations:

Publications have been submitted on this subproject: View all 62 publications for this subprojectView all 169 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 43 journal articles for this subprojectView all 122 journal articles for this center

Supplemental Keywords:

respiratory tract, extrapulmonary organs,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, particulate matter, Toxicology, Health Risk Assessment, Risk Assessments, Physical Processes, atmospheric particulate matter, acute cardiovascular effects, atmospheric particles, airway disease, exposure, animal model, ambient particle health effects, ultrafine particulate matter, atmospheric aerosol particles, inhalation toxicology, PM, cardiovascular disease

Progress and Final Reports:

2006 Progress Report
2007 Progress Report
2008 Progress Report
2009 Progress Report
2010 Progress Report
2011 Progress Report
Final Report


Main Center Abstract and Reports:

R832415    Rochester PM Center

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832415C001 Characterization and Source Apportionment
R832415C002 Epidemiological Studies on Extra Pulmonary Effects of Fresh and Aged Urban Aerosols from Different Sources
R832415C003 Human Clinical Studies of Concentrated Ambient Ultrafine and Fine Particles
R832415C004 Animal models: Cardiovascular Disease, CNS Injury and Ultrafine Particle Biokinetics
R832415C005 Ultrafine Particle Cell Interactions In Vitro: Molecular Mechanisms Leading To Altered Gene Expression in Relation to Particle Composition