Chronic intermittent electronic cigarette exposure induces cardiac dysfunction and atherosclerosis in apolipoprotein-E knockout mice

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 317; no. 2; pp. H445 - H459
• Main Authors: Espinoza-Derout, Jorge, Hasan, Kamrul M., Shao, Xuesi M., Jordan, Maria C., Sims, Carl, Lee, Desean L., Sinha, Satyesh, Simmons, Zena, Mtume, Norma, Liu, Yanjun, Roos, Kenneth P., Sinha-Hikim, Amiya P., Friedman, Theodore C.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2019
• Series: Integrative Cardiovascular Physiology and Pathophysiology
• Subjects: Abnormalities; Animals; Apolipoprotein E; Apolipoproteins; Arteriosclerosis; Atherosclerosis; Atherosclerosis - etiology; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; Cardiomyocytes; Cardiomyopathy; Cigarettes; Circadian rhythms; Deoxyribonucleic acid; Disease Models, Animal; DNA; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; Electronic cigarettes; Electronic Nicotine Delivery Systems; Exposure; Inhalation Exposure - adverse effects; Lesions; Male; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Mitochondrial DNA; Mutation; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - ultrastructure; Nicotine; Nicotine - toxicity; Nicotinic Agonists - toxicity; Oxidative Stress; Plaque, Atherosclerotic; Reactive Oxygen Species - metabolism; Smoking; Stroke Volume; Transcriptome; Transmission electron microscopy; Vaping - adverse effects; Ventricle; Ventricular Dysfunction, Left - etiology; Ventricular Dysfunction, Left - genetics; Ventricular Dysfunction, Left - metabolism; Ventricular Dysfunction, Left - physiopathology; Ventricular Function, Left; atherosclerosis; cardiovascular disease; cardiomyopathy; inflammation; myocardial biology
• ISSN: 0363-6135; 1522-1539; 1522-1539
• DOI: 10.1152/ajpheart.00738.2018

Electronic cigarettes (e-cigarettes), also known as electronic nicotine delivery systems, are a popular alternative to conventional nicotine cigarettes, both among smokers and those who have never smoked. In spite of the widespread use of e-cigarettes and the proposed detrimental cardiac and atherosclerotic effects of nicotine, the effects of e-cigarettes on these systems are not known. In this study, we investigated the cardiovascular and cardiac effects of e-cigarettes with and without nicotine in apolipoprotein-E knockout (ApoE −/− ) mice. We developed an e-cigarette exposure model that delivers nicotine in a manner similar to that of human e-cigarettes users. Using commercially available e-cigarettes, bluCig PLUS, ApoE −/− mice were exposed to saline, e-cigarette without nicotine [e-cigarette (0%)], and e-cigarette with 2.4% nicotine [e-cigarette (2.4%)] aerosol for 12 wk. Echocardiographic data show that mice treated with e-cigarette (2.4%) had decreased left ventricular fractional shortening and ejection fraction compared with e-cigarette (0%) and saline. Ventricular transcriptomic analysis revealed changes in genes associated with metabolism, circadian rhythm, and inflammation in e-cigarette (2.4%)-treated ApoE −/− mice. Transmission electron microscopy revealed that cardiomyocytes of mice treated with e-cigarette (2.4%) exhibited ultrastructural abnormalities indicative of cardiomyopathy. Additionally, we observed increased oxidative stress and mitochondrial DNA mutations in mice treated with e-cigarette (2.4%). ApoE −/− mice on e-cigarette (2.4%) had also increased atherosclerotic lesions compared with saline aerosol-treated mice. These results demonstrate adverse effects of e-cigarettes on cardiac function in mice. NEW & NOTEWORTHY The present study is the first to show that mice exposed to nicotine electronic cigarettes (e-cigarettes) have decreased cardiac fractional shortening and ejection fraction in comparison with controls. RNA-seq analysis reveals a proinflammatory phenotype induced by e-cigarettes with nicotine. We also found increased atherosclerosis in the aortic root of mice treated with e-cigarettes with nicotine. Our results show that e-cigarettes with nicotine lead to detrimental effects on the heart that should serve as a warning to e-cigarette users and agencies that regulate them.