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

Am J Physiol Heart Circ Physiol. 2019 Aug 1;317(2):H445-H459. doi: 10.1152/ajpheart.00738.2018. Epub 2019 Jun 7.


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.

Keywords: atherosclerosis; cardiomyopathy; cardiovascular disease; inflammation; myocardial biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / etiology*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Disease Models, Animal
  • Electronic Nicotine Delivery Systems*
  • Inhalation Exposure / adverse effects
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Mutation
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / ultrastructure
  • Nicotine / toxicity*
  • Nicotinic Agonists / toxicity*
  • Oxidative Stress
  • Plaque, Atherosclerotic
  • Reactive Oxygen Species / metabolism
  • Stroke Volume*
  • Transcriptome
  • Vaping / adverse effects*
  • Ventricular Dysfunction, Left / etiology*
  • Ventricular Dysfunction, Left / genetics
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left*


  • DNA, Mitochondrial
  • Nicotinic Agonists
  • Reactive Oxygen Species
  • Nicotine