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Cigarette smoke increases cardiomyocyte ceramide accumulation and inhibits mitochondrial respiration.
MedLine Citation:
PMID:  25416336     Owner:  NLM     Status:  Publisher    
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
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
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-22
Journal Detail:
Title:  BMC cardiovascular disorders     Volume:  14     ISSN:  1471-2261     ISO Abbreviation:  BMC Cardiovasc Disord     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-22     Completed Date:  -     Revised Date:  2014-11-25    
Medline Journal Info:
Nlm Unique ID:  100968539     Medline TA:  BMC Cardiovasc Disord     Country:  -    
Other Details:
Languages:  ENG     Pagination:  165     Citation Subset:  -    
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