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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\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) 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\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    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\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    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\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    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.\n                  <\/jats:p>\n                  <jats:p>NEW &amp; 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.<\/jats:p>","DOI":"10.1152\/ajpheart.00738.2018","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T11:31:37Z","timestamp":1559907097000},"page":"H445-H459","source":"Crossref","is-referenced-by-count":96,"title":["Chronic intermittent electronic cigarette exposure induces cardiac dysfunction and atherosclerosis in apolipoprotein-E knockout mice"],"prefix":"10.1152","volume":"317","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8222-5227","authenticated-orcid":false,"given":"Jorge","family":"Espinoza-Derout","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles R. 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