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Executive Summary: Variation in Susceptibility to Ozone-Induced Health Effects in Rodent Models of Cardiometabolic Disease
Citation:
Dye, J., D. Costa, AND U. Kodavanti. Executive Summary: Variation in Susceptibility to Ozone-Induced Health Effects in Rodent Models of Cardiometabolic Disease. INHALATION TOXICOLOGY. Informa Healthcare USA, New York, NY, 27(1):105-15, (2015).
Impact/Purpose:
The causes of susceptibility variations remain unidentified and therefore, it is difficult to develop approaches for risk refinement for susceptible subgroups. This comprehensive research approach with systems biology concept compares diverse CVD models and provides information on causes of variation in susceptibility, and risk factors exacerbating adverse health outcomes. Through this research project, it is possible to identify which underlying CVD condition might be critical in exacerbating ozone health effects, and the risk factors that are critical in determining susceptibility variations. This information could be used in developing strategies to identify at risk populations among diverse CVD and other ailments, and develop preventive measures. This approach can be used with other pollutants to determine how these risk factors are influenced and if there is a commonality in the mechanism of susceptibility variations across different pollution mixtures.
Description:
Seven million premature deaths occur annually due to air pollution worldwide, of which ~80% are attributed to exacerbation of cardiovascular disease (CVD}, necessitating greater attention to understanding the causes of susceptibility to air pollution in this sector of population. We used rat models of CVD with or without obesity and compared them to healthy strains to examine the risk factors of ozone-induced lung injury and inflammation. We examined functional, biochemical and molecular changes in several organs to evaluate how physiological factors as well as compensatory antioxidant reserves modulate processes by which ozone injury is influenced by underlying disease. In this study, we highlight key findings of this series of reports. We show that underlying cardiopulmonary insufficiency in genetically predisposed rats appears to increase the effective ozone dose; thus dosimetry is one factor contributing to exacerbated ozone effects. We further show that antioxidant reserve in airway lining fluid modulates ozone-induced damage such that strains with the least antioxidant reserve incur the greatest injury. And finally,we show that the inflammatory response to ozone is governed by a cluster of genes involved in regulating cytokine release, trafficking of inflammatory cells and processes related to cellular apoptosis and growth. All such processes are influenced not only by ozone dosimetry and the lung antioxidant milieu but also by the strain-specific genetic factors. In using a comprehensive systems biology research approach, our data reveal key risk factors for - and strategies to reduce risk of - air pollution mortality among those with CVD.
