Ceramide is necessary for cigarette smoke‐induced reduced heart mitochondrial function (LB649)

Cigarette smoke exposure increases risk of multiple cardiovascular complications, including heart failure, heart attack, and atherosclerosis. Given that ceramides are both produced in the lung with smoke exposure and are known to alter cardiovascular function, we hypothesized that ceramides may mediate the deleterious effect of smoking on heart mitochondrial function. Employing cell and animal models, we explored the effect of cigarette smoke on myocardial cell mitochondrial function. Muscle cells were treated with conditioned media from cigarette smoke extract (CSE)‐exposed lung cells, followed by analysis of ceramides and assessment of mitochondrial function. H9C2 cardiomyocytes cells treated with CSE‐exposed conditioned medium suffered a dramatic reduction in mitochondrial respiration. These effects were mitigated when lung cells were treated with the ceramide inhibitor myriocin prior to and during CSE exposure. Mice were exposed to daily cigarette smoke for 12 wk and received either PBS or myriocin injections. At the conclusion of the period, heart ceramide and mitochondrial function was determined. Daily cigarette smoke exposure in PBS‐, but not myriocin‐treated animals, resulted in elevated heart ceramide levels and reduced ceramide mitochondrial respiration. Thus, ceramide inhibition appears to prevent heart mitochondrial dysfunction with smoke exposure.