Cigarette Smoke Affects Genes Associated with Heart and Lung Health
Joel Pounds, Ph.D.
Pacific Northwest National Laboratory
NIEHS Grant U54ES016015
An NIEHS-funded mouse study provides evidence that sidestream cigarette smoke affects the activity of hundreds of genes that protect the heart and lungs. Obese mice on a high-fat diet showed the strongest response after inhaling sidestream smoke.
Smoking and obesity are risk factors for cardiovascular disease, but the molecular mechanisms behind the increased risks are not well understood. The researchers used mouse models to study early signaling events that occur in the heart and lungs after cigarette smoke exposure. They also looked at the role of obesity in this response. The investigators exposed normal weight and obese mice fed a high-fat diet to the two components of second hand smoke: exhaled mainstream smoke and the side stream smoke emitted from the burning tip, the latter of which makes up 85 percent of second smoke.
Using whole genome microarray analysis, the investigators found that mice exposed to mainstream smoke showed cellular and molecular inflammatory responses in the lung. The normal weight animals had 1,466 differentially expressed pulmonary genes (p < 0.01) and 463 differentially expressed cardiac genes. Exposures to sidestream smoke brought a weak pulmonary response (328 genes) but a strong cardiac response (1,590 genes). In general, the most sensitive smoke-induced cardiac transcriptional changes observed in the normal weight mice were not observed in the smoke-exposed obese mice. The smoke exposure also suppressed multiple proteome maintenance genes induced in the hearts of obese mice. Overall, the results showed that the heart is sensitive to sidestream smoke and that adaptive responses in healthy mice were absent in obese mice.
Citation: Tilton SC, Karin NJ, Webb-Robertson BJ, Waters KM, Mikheev V, Lee KM, Corley RA, Pounds JG, Bigelow DJ. 2013. Impaired Transcriptional Response of the Murine Heart to Cigarette Smoke in the Setting of High Fat Diet and Obesity. Chem Res Toxicol 26 (7):1034–1042.
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