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Pulmonary Transcriptional Response to Ozone in Healthy and Cardiovascular Compromised Rat Models
Citation:
Ward, W. AND U. Kodavanti. Pulmonary Transcriptional Response to Ozone in Healthy and Cardiovascular Compromised Rat Models. INHALATION TOXICOLOGY. Informa Healthcare USA, New York, NY, 27(1):93-104, (2015).
Impact/Purpose:
Susceptibility variation to air pollution induced health effects are encountered but the mechanisms are poorly understood. This study used comparative transcriptional approach to understand variation in ozone induced lung injury in rat models of cardiovascular diseases (CVD). A snapshot analysis of comparative expression profiling suggests that the pulmonary responsiveness of the various CVD strains was linked to the defining gene profiles of the individual cardiac models. From expression profiling of the lung it appeared that mechanistic differences at expression level confer the variations in susceptibility to ozone-induced lung injury among rats with diverse underlying cardiometabolic complications.
Description:
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, atherosderosis-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 .
