Pulmonary transcriptional response to ozone in healthy and cardiovascular compromised rat models

Abstract

The genetic cardiovascular disease (CVD) and associated metabolic impairments can influence the lung injury from inhaled pollutants. We hypothesized that comparative assessment of global pulmonary expression profile of healthy and CVD-prone rat models will provide mechanistic insights into susceptibility differences to ozone. The lung expression profiles of healthy Wistar Kyoto (WKY) and CVD-compromised spontaneously hypertensive (SH), stroke-prone SH (SHSP), obese SH heart failure (SHHF) and obese, atherosclerosis-prone JCR rats were analyzed using Affymetrix platform immediately after 4-h air or 1 ppm ozone exposure. At baseline, the JCR exhibited the largest difference in the number of genes among all strains when compared with WKY. Interestingly, the number of genes affected by ozone was inversely correlated with genes different at baseline relative to WKY. A cluster of NFkB target genes involved in cell-adhesion, antioxidant response, inflammation and apoptosis was induced in all strains, albeit at different levels (JCR < WKY < SHHF < SH < SHSP). The lung metabolic syndrome gene cluster indicated expressions in opposite directions for SHHF and JCR suggesting different mechanisms for common disease phenotype and perhaps obesity-independent contribution to exacerbated lung disease. The differences in expression of adrenergic receptors and ion-channel genes suggested distinct mechanisms by which ozone might induce protein leakage in CVD models, especially SHHF and JCR. Thus, the pulmonary response to ozone in CVD strains was likely linked to the defining gene expression profiles. Differential transcriptional patterns between healthy and CVD rat strains at baseline, and after ozone suggests that lung inflammation and injury might be influenced by multiple biological pathways affecting inflammation gene signatures.

• Air pollution
• cardiovascular disease models
• lung injury
• metabolic syndrome
• ozone
• transcriptional profiling

Acknowledgements and disclaimer

We are grateful to Dr Daniel L. Costa, Dr Barbara Buckley and Dr. Cristal Bowman (U.S. EPA) for their critical review of this manuscript. The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency and approved for publication. Approval does neither 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.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Supplementary material available online

Supplemental Tables 1-10.