Abstract P292: Possible Mechanism and Potential Markers for Ozone-Induced Cardiac Toxicity

Abstract

A significant number of deaths each year in the US have been linked to environmental pollutants such as ozone (O₃). Earlier studies from our laboratory have shown that myocardial dysfunction, subsequent to chronic O₃ exposure, in normal adult rats may be associated with a decrease in antioxidant reserve and with an increased activity of inflammatory mediators. The present study tested the hypothesis that O₃ induced cardiac dysfunction in healthy normal adult rats may be due to changes in caveolin-1 and caveolin-3 levels. Sprague Dawley rats were exposed 8 hr/day for 28 and 56 days to filtered air or 0.8 ppm O₃. In order to assess the chronic effects to O₃, in-vivo cardiac function was assessed by measuring left ventricular developed pressure (LVDP), 24 hr after termination of O₃ exposure. Compared to rats exposed to filtered air, LVDP values significantly decreased in all O₃ exposed animals. This attenuation of cardiac function was associated with increased myocardial TNF-alpha (TNF-α) levels and decreased myocardial activities of superoxidase dismutase (SOD). Progressive increases in the expression of myocardial TNF-α in 4 and 8 week O₃ exposed animals were followed by decreases in cardiac caveolin-1 levels. However, differential changes in the expression of caveolin-3 in hearts from 4 and 8 week O₃ exposed animals were independent of intra-cardiac TNF-α levels. These novel findings suggest the interesting possibility that a balance between caveolin-1 and caveolin-3 may be involved in O₃- mediated cardiac toxicity. Furthermore, differential changes in caveolin-3 content may serve as a marker that predicts moderate and chronic stages of cardiac injury specific to exposure to O₃ in human populations residing in urban areas with unhealthy levels of O₃. The study is timely and has clinical significance related to environmental causes of cardiovascular disease. This novel study will form a basis for future studies to understand and define the various components of the mechanistic cascade responsible for generation of cell death signaling subsequent to O₃ exposure. The long-term goal of this study is in guiding regulatory policies to the USEPA regarding air quality standards pertaining to O₃ levels.