Abstract P292: Possible Mechanism and Potential Markers for Ozone-Induced Cardiac Toxicity
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.
- © 2011 by American Heart Association, Inc.