Long-Term Electronic Cigarette Exposure Induces Cardiovascular Dysfunction Similar to Tobacco Cigarettes: Role of Nicotine and Exposure Duration

Electronic cigarette (e-cig) vaping (ECV) has been proposed as a safer alternative to tobacco cigarette smoking (TCS); however, this remains controversial due to a lack of long-term comparative studies. Therefore, we developed a chronic mouse exposure model, which mimics human vaping and allows comparison to TCS. Longitudinal studies were performed to evaluate alterations in cardiovascular function with TCS and ECV exposure durations of up to 60 weeks. For ECV, e-cig liquid with box-mod were used and for TCS, 3R4F-cigarettes. C57/BL6 male mice were exposed 2 hours/day, 5 days/week to TCS, ECV, or air-control. The role of vape nicotine levels was evaluated using e-cig-liquids with 0, 6 or 24 mg/ml nicotine. Following 16 weeks exposure, increased constriction to phenylephrine and impaired endothelium-dependent and endothelium-independent vasodilation were observed in aortic segments, paralleling the onset of systemic hypertension, with elevations in systemic vascular resistance. Following 32 weeks, TCS and ECV induced cardiac hypertrophy. All of these abnormalities further increased out to 60 weeks of exposure, with elevated heart weight and aortic thickness along with increased superoxide production in vessels and cardiac tissues of both ECV and TCS mice. While ECV-induced abnormalities were seen in the absence of nicotine, these occurred earlier and were more severe with higher nicotine exposure. Thus, long-term vaping of e-cig, can induce cardiovascular disease similar to TCS, and the severity of this toxicity increases with exposure duration and vape nicotine content.