2 research outputs found
Impaired Transcriptional Response of the Murine Heart to Cigarette Smoke in the Setting of High Fat Diet and Obesity
Smoking and obesity are each well-established
risk factors for
cardiovascular heart disease, which together impose earlier onset
and greater severity of disease. To identify early signaling events
in the response of the heart to cigarette smoke exposure within the
setting of obesity, we exposed normal weight and high fat diet-induced
obese (DIO) C57BL/6 mice to repeated inhaled doses of mainstream (MS)
or sidestream (SS) cigarette smoke administered over a two week period,
monitoring effects on both cardiac and pulmonary transcriptomes. MS
smoke (250 μg wet total particulate matter (WTPM)/L, 5 h/day)
exposures elicited robust cellular and molecular inflammatory responses
in the lung with 1466 differentially expressed pulmonary genes (<i>p</i> < 0.01) in normal weight animals and a much-attenuated
response (463 genes) in the hearts of the same animals. In contrast,
exposures to SS smoke (85 μg WTPM/L) with a CO concentration
equivalent to that of MS smoke (∼250 CO ppm) induced a weak
pulmonary response (328 genes) but an extensive cardiac response (1590
genes). SS smoke and to a lesser extent MS smoke preferentially elicited
hypoxia- and stress-responsive genes as well as genes predicting early
changes of vascular smooth muscle and endothelium, precursors of cardiovascular
disease. The most sensitive smoke-induced cardiac transcriptional
changes of normal weight mice were largely absent in DIO mice after
smoke exposure, while genes involved in fatty acid utilization were
unaffected. At the same time, smoke exposure suppressed multiple proteome
maintenance genes induced in the hearts of DIO mice. Together, these
results underscore the sensitivity of the heart to SS smoke and reveal
adaptive responses in healthy individuals that are absent in the setting
of high fat diet and obesity
Impaired Transcriptional Response of the Murine Heart to Cigarette Smoke in the Setting of High Fat Diet and Obesity
Smoking and obesity are each well-established
risk factors for
cardiovascular heart disease, which together impose earlier onset
and greater severity of disease. To identify early signaling events
in the response of the heart to cigarette smoke exposure within the
setting of obesity, we exposed normal weight and high fat diet-induced
obese (DIO) C57BL/6 mice to repeated inhaled doses of mainstream (MS)
or sidestream (SS) cigarette smoke administered over a two week period,
monitoring effects on both cardiac and pulmonary transcriptomes. MS
smoke (250 μg wet total particulate matter (WTPM)/L, 5 h/day)
exposures elicited robust cellular and molecular inflammatory responses
in the lung with 1466 differentially expressed pulmonary genes (<i>p</i> < 0.01) in normal weight animals and a much-attenuated
response (463 genes) in the hearts of the same animals. In contrast,
exposures to SS smoke (85 μg WTPM/L) with a CO concentration
equivalent to that of MS smoke (∼250 CO ppm) induced a weak
pulmonary response (328 genes) but an extensive cardiac response (1590
genes). SS smoke and to a lesser extent MS smoke preferentially elicited
hypoxia- and stress-responsive genes as well as genes predicting early
changes of vascular smooth muscle and endothelium, precursors of cardiovascular
disease. The most sensitive smoke-induced cardiac transcriptional
changes of normal weight mice were largely absent in DIO mice after
smoke exposure, while genes involved in fatty acid utilization were
unaffected. At the same time, smoke exposure suppressed multiple proteome
maintenance genes induced in the hearts of DIO mice. Together, these
results underscore the sensitivity of the heart to SS smoke and reveal
adaptive responses in healthy individuals that are absent in the setting
of high fat diet and obesity