1. Chronic intermittent electronic cigarette exposure induces cardiac dysfunction and atherosclerosis in apolipoprotein-E knockout mice.
- Author
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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, and Friedman, Theodore C
- Subjects
Myocytes ,Cardiac ,Animals ,Mice ,Inbred C57BL ,Ventricular Dysfunction ,Left ,Disease Models ,Animal ,Reactive Oxygen Species ,Nicotine ,DNA ,Mitochondrial ,Nicotinic Agonists ,Stroke Volume ,Inhalation Exposure ,Oxidative Stress ,Ventricular Function ,Left ,Mutation ,Male ,Atherosclerosis ,Plaque ,Atherosclerotic ,Transcriptome ,Vaping ,Mice ,Knockout ,ApoE ,Electronic Nicotine Delivery Systems ,atherosclerosis ,cardiomyopathy ,cardiovascular disease ,inflammation ,myocardial biology ,Myocytes ,Cardiac ,Mice ,Inbred C57BL ,Ventricular Dysfunction ,Left ,Disease Models ,Animal ,DNA ,Mitochondrial ,Ventricular Function ,Plaque ,Atherosclerotic ,Knockout ,ApoE ,Physiology ,Medical Physiology ,Cardiovascular System & Hematology - Abstract
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.
- Published
- 2019