Cardiovascular Effects of Particles:The Role of Oxidative Stress and Metal Pathw

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DESCRIPTION (provided by applicant): Since the late 1980s, studies of acute and chronic exposure to particulate air pollution have shown it to be associated with early death. It was quickly apparent that most of these early deaths were from cardiovascular disease. Definition of the underlying mechanisms that may explain the epidemiological findings of cardiac mortality/morbidity associated with exposure to ambient particles, definition of subpopulation at increased risk of adverse health outcomes from particulate matter, and understanding the differential toxicity of different types of particles are among the research priorities defined by the U. S. National Research Council. We propose to examine the association of different types and sources of particle exposure with cardiovascular and pulmonary responses along a mechanistic pathway, using data from the Normative Aging Study, a prospective cohort study conducted by the Veterans Administration in the greater Boston area. Specifically, we will examine whether short term changes in automatic function, as indexed by heart rate variability, are associated with particle exposure, and determine whether that effect is mediated by part by oxidative stress and metal toxicity by examining effect modification by genotypes that modify defenses against oxidative stress and metal handling. We will similarly examine associations, and effect modification, for vascular function, as indexed by a non-invasive pulse Doppler measures of arterial compliance and blood pressure, and examine a direct association with systemic markers of inflammation and oxidative stress (c reactive protein, Sicam, Svcam, homocysteine, and 8-hydroxyguanosine.