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

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.

Vaping Cardiovascular Health Risks: an Updated Umbrella Review

“…Our umbrella review, poignantly synthesizing the evidence accrued so far from in vitro, in animal, in human volunteers, healthy subjects, and patients on the cardiovascular risk associated with EVC use, either acute or chronic, shows that data are expanding progressively, but several conclusions can already be made on the [25,32]. For instance, oxidative stress, cytotoxicity, and cardiomyocyte dysfunction are established effects of EVC [33]. Second, EVC impact adversely on BP management, cause tachycardia, and worsen arterial stiffness [19,34].…”

Nicotine in Senescence and Atherosclerosis

“…They found that nicotine caused impaired, ventricular systolic, but not diastolic, function in the heart. In addition, ROS, mitochondrial DNA damage, and plaque in the aortic root were significantly higher [247].…”

How bad are e‐cigarettes? What can we learn from animal exposure models?

“…Many groups have measured cotinine, the more metabolically stable metabolite of nicotine, in blood and urine for comparison with human exposure levels. In four studies that quantified urinary cotinine, three had levels indicative of heavy smoking (McGrath-Morrow et al 2015;Ponzoni et al 2015;Lauterstein et al 2016) and one of light smoking (Olfert et al 2018), while studies measuring serum (Smith et al 2015;Sussan et al 2015;Garcia-Arcos et al 2016;Alasmari et al 2017;Laube et al 2017;Rau et al 2017;Chen et al 2018a;Crotty Alexander et al 2018) or plasma (McGrath-Morrow et al 2015;Qasim et al 2018;Espinoza-Derout et al 2019a) cotinine levels (range 9-611 ng ml −1 ) were equivalent to the range observed in active smokers (Hukkanen et al 2005). Of course, not all e-liquids contain nicotine and the nicotine content of e-liquids employed in animal studies has varied from 12 to 33 mg ml −1 (Table 1).…”