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01.12.2014 | Research article | Ausgabe 1/2014 Open Access

BMC Cardiovascular Disorders 1/2014

Cigarette smoke increases cardiomyocyte ceramide accumulation and inhibits mitochondrial respiration

BMC Cardiovascular Disorders > Ausgabe 1/2014
Trevor S Tippetts, Duane R Winden, Adam C Swensen, Michael B Nelson, Mikayla O Thatcher, Rex R Saito, Tyler B Condie, Kurtis J Simmons, Allan M Judd, Paul R Reynolds, Benjamin T Bikman
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1471-2261-14-165) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

TST, MBN, MOT, RRS, TBC, KJS conducted cell culture studies. TST, DRW, MBN, MOT, RRS, TBC, KJS performed animal studies. TST, ACS, MOT isolated and quantified ceramides. TST, BTB performed mitochondrial assays. PRR provided technical expertise with sidestream cigarette smoke studies. AMJ, BTB conceived of the study. BTB prepared the manuscript. All authors read and approved the final manuscript.



Cigarette smoking is a common and lethal worldwide habit, with considerable mortality stemming from its deleterious effects on heart function. While current theories posit altered blood lipids and fibrinogen metabolism as likely mediators, none have explored the role of the sphingolipid ceramide in exacerbating heart function with smoke exposure. Ceramide production is a consequence of cigarette smoke in the lung, and considering ceramide’s harmful effects on mitochondrial function, we sought to elucidate the role of ceramide in mediating smoke-induced altered heart mitochondrial respiration.


Lung cells (A549) were exposed to cigarette smoke extract (CSE) and heart cells (H9C2) were exposed to the lung-cell conditioned medium. Adult male mice were exposed sidestream cigarette smoke for 8 wk with dietary intervention and ceramide inhibition. Ceramides and heart cell or myocardial mitochondrial respiration were determined.


Lung cell cultures revealed a robust response to cigarette smoke extract in both production and secretion of ceramides. Heart cells incubated with lung-cell conditioned medium revealed a pronounced inhibition of myocardial mitochondrial respiration, though this effect was mitigated with ceramide inhibition via myriocin. In vivo, heart ceramides increased roughly 600% in adult mice with long-term sidestream cigarette smoke exposure. This resulted in a significant ceramide-dependent reduction in left myocardial mitochondrial respiration, as heart mitochondria from the mice exposed to both smoke and myriocin injections respired normally.


These results suggest ceramide to be an important mediator of altered myocardial mitochondrial function with cigarette smoke exposure. Thus, anti-ceramide therapies might be considered in the future to protect heart mitochondrial function with smoke exposure.
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