Executive Summary: variation in susceptibility to ozone-induced health effects in rodent models of cardiometabolic disease

Abstract

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.

• Cardiovascular disease
• hypertension
• obesity
• ozone
• rat models
• susceptibility

Acknowledgements

We are grateful to Drs. Stephen Gavett and Gary Hatch (US EPA) for their critical review of this manuscript. We are indebted to late Dr. Donald Gardner for his critical assistance and dedication to this special edition on susceptibility to air pollution.

Declaration of interest

The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and the policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.