Abstract 11199: Oxidative Stress in the Heart Correlates With Changes in Cardiac Gene Expression Patterns in Rats Chronically Exposed to Ambient Air Pollutants
Introduction: Recently we reported up-regulated expression in cardiac genes for thioredoxin interacting protein (Txnip) and cytochrome P450 (Cyp2e1) in rats chronically exposed to coarse and ultrafine particles. Txnip is a pro-oxidant factor, which inhibits thioredoxin, a major antioxidant protein in mammals. Cyp2e1 plays a significant role in the metabolism of toxic constituents of particulate air pollutants (e.g. volatile organic compound), and yields metabolites with increased toxicity.
Hypothesis: Our hypothesis was that the magnitude of oxidative stress in rat hearts chronically exposed to air pollutants would influence specific changes in gene expression patterns in the heart.
Methods: Heart tissue was obtained from male F344 rats which were for exposed for 3 month to filtered air (FA), coarse (CP), fine (FP) and ultrafine (UFP) particles (n=8 per group) in a particle concentrator equipped mobile unit located near a major freeway. Cardiac tissue was subjected to gene expression profiling (Illumina BeadChips) and analyzed for total (free and protein bound) MDA levels.
Results: Txnip and Cyp2e1 expressions were increased in the CP and UFP groups vs. the FA group with average fold ratio of >1.5. MDA tended to be higher in the CP and UFP groups (19.6±2.4, and 20.7±4.9 nmol/g of tissue respectively) vs. the FA (15.2±3.0 nmol/g) or FP (12.2±1.3 nmol/g) groups. MDA concentration significantly and positively correlated with Txnip (r=0.498, p=0.0083) and Cyp2e1( r=0.548, p=0.0031) expression levels.
Conclusion: These results demonstrate for the first time that the level of oxidative stress due to air pollution correlates with the extent of genetic changes, and supports the concept that oxidative stress plays a major role in the cardiotoxic effects of air pollution.
- © 2010 by American Heart Association, Inc.