Abstract

Smoking is the major cause of cardiovascular diseases (CVD) and is the single largest cause of death in the USA. Smoking cessation can reduce the mortality from CVD. Electronic cigarettes, also known as electronic nicotine delivery systems (ENDS), have been marketed as a smoking cessation device. In spite of the widespread use of ENDS and the proposed detrimental cardiac and atherosclerotic effects of nicotine, the effects of ENDS on these systems are not well known. Recently, using Apolipoprotein E null mice, we demonstrated that mice exposed to e-cigarettes have decreased cardiac fractional shortening and ejection fraction together with ventricular ultrastructural abnormalities indicative of cardiomyopathy in comparison with controls. In this study, we investigated the detrimental effects of ENDS at doses similar to the clinically relevant concentrations found in habitual smokers and a high fat diet (HFD) on cardiac structure and function in a commonly used model of diet-induced obesity. C57 BL6 mice fed HFD were exposed to ENDS in the presence (2.4%) or absence (0%) of nicotine and saline aerosol for 12 weeks. Mice exposed to ENDS (2.4%) had increased serum free fatty acid levels in comparison with saline and ENDS (0%). Echocardiographic data show that mice treated with ENDS (2.4%) had decreased left ventricular fractional shortening and ejection fraction compared to ENDS (0%) and saline. Transmission electron microscopy revealed that cardiomyocytes of mice treated with ENDS (2.4%) exhibited ventricular abnormalities, including lipid accumulation (ventricular steatosis), myofibrillar derangement and destruction, and mitochondrial hypertrophy. Additionally, ENDS (2.4%) also caused increased cardiac oxidative stress and triggered cardiomyocyte apoptosis. These results demonstrate profound adverse effects of ENDS on ventricular structure and function in obese mice. We surmise that ENDS exposure may cause heart failure and other forms of cardiomyopathy in obese patients. This is important information for patients that use ENDS and regulatory agencies that regulate ENDS.

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