Mast Cell Mediated Cardiac Effects of Particulate Matter

EPA Grant Number: R831953
Title: Mast Cell Mediated Cardiac Effects of Particulate Matter
Investigators: Brower, Gregory L. , Gardner, Jason D. , Janicki, Joseph S. , McDonald, Jacob D.
Current Investigators: Brower, Gregory L. , Gardner, Jason D. , Janicki, Joseph S. , McDonald, Jacob D. , Murray, David B.
Institution: Auburn University Main Campus , Lovelace Respiratory Research Institute , University of South Carolina at Columbia
Current Institution: University of South Carolina at Columbia , Lovelace Respiratory Research Institute
EPA Project Officer: Hunt, Sherri
Project Period: October 1, 2005 through September 30, 2007
Project Amount: $501,250
RFA: The Role of Air Pollutants in Cardiovascular Disease (2003) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Air , Particulate Matter , Health Effects

Objective:

The overall objective of this project is to elucidate the mechanisms responsible for the relationship between particulate matter (PM) exposure and untoward cardiovascular events. Towards this end the following overall hypothesis will be tested: the greater incidence of adverse cardiovascular events associated with increased exposure to PM involves cardiac mast cell degranulation which in turn causes extracellular matrix degradation, ventricular dilatation and reduced cardiac function.

Approach:

The project consists of two specific aims that are designed to test this hypothesis. Throughout the project, our well characterized model of congestive heart failure (CHF) secondary to chronic ventricular volume overload in rats will be utilized. Heart failure is induced by creating an infrarenal aortocaval fistula. The primary objective of this proposal is to determine the contribution of PM mediated mast cell activation to the increased morbidity/mortality due to CHF. In order to determine if individuals are more susceptible to PM mediated cardiac dysfunction, rats in the compensated phase of CHF will undergo controlled acute or repeated exposure to diesel exhaust for six hours/day during the progressive development of CHF. At the end of the study period, in vivo hemodynamics, ventricular function, exercise capacity and in vitro diastolic and systolic function will be evaluated. Subsequent histology and biochemical analysis will be performed to evaluate the status of the extracellular matrix; cytokine levels; mast cell density, stage distribution and function; and matrix metalloproteinase activity. The effect of PM exposure on morbidity and mortality will also be assessed. Finally pharmacologic studies will be performed to determine if the adverse effects of PM exposure can be attenuated or prevented.

Expected Results:

Upon completion of this project, the following questions pertaining to this request for proposal will be answered: 1) does PM exposure accelerate progression to congestive heart failure?; 2) does the cardiac mast cell mediate the adverse cardiac influence of PM exposure?; and 3) can the negative cardiac consequences of PM exposure be attenuated or prevented using pharmacological compounds which prevent mast cell degranulation or antagonize endothelin-1?

Publications and Presentations:

Publications have been submitted on this project: View all 13 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 1 journal articles for this project

Supplemental Keywords:

ambient air, exposure, risk assessment, health effects, vulnerability, enzymes, cumulative effects, pathology, RFA, Health, Scientific Discipline, Air, particulate matter, Toxicology, air toxics, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Biology, copollutant exposures, atmospheric particulate matter, airway epithelial cells, cardiopulmonary responses, fine particles, acute lung injury, exposure, air pollution, susceptible subpopulations, endothelial function, chronic health effects, ultrafine particulate matter, lung inflammation, oxidant gas, particulate exposure, heart rate, Acute health effects, inhaled, cardiotoxicity, cardiopulmonary, oxidant stress, ultrafine particles, concentrated particulate matter, cardiovascular disease

Progress and Final Reports:

2005 Progress Report
Final Report