Role of Nicotine and Exposure Duration in the Cardiovascular Toxicity of Electronic Cigarettes and Tobacco Cigarettes in a Long‐term Mouse Exposure Model

Abstract

Background 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 and applied a chronic mouse exposure model, which mimics human vaping and allows comparison to TCS. This model was applied to determine the role of nicotine levels and exposure duration in the onset of cardiovascular changes and toxicity. Methods 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 formulations were used with box-mod 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. Results Following 16 weeks of exposure, increased constriction to phenylephrine and impaired endothelial-dependent and endothelial-independent vasodilation were observed in aortic segments of the TCS and ECV exposure groups. This paralleled the onset of systemic hypertension, with elevations in systemic vascular resistance. These changes were seen in all ECV and TCS exposed groups but were most severe with TCS and ECV with 24 mg/ml nicotine. Following 32 weeks, TCS and ECV induced cardiac hypertrophy with concentric left ventricular wall thickening. All of these abnormalities further increased out to 60 weeks of exposure, with elevated heart weight and aortic wall thickness along with increased superoxide production measured in vessels and cardiac tissues of both ECV and TCS mice. Conclusion 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.