Long-term electronic cigarette exposure induces cardiovascular dysfunction similar to tobacco cigarettes: role of nicotine and exposure duration

Abstract

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.

Structural and functional remodeling of the female Apoe−/− mouse aorta due to chronic cigarette smoke exposure

“…In agreement with findings by El-Mahdy et al (36), chronic inhalation of cigarette smoke promoted diffuse thickening of the aorta (Fig. 3H and Supplemental Tables S1 and S2).…”

“…Throughout the second half of the study, blood pressure in cigarette-exposed mice remained stable around values that exceeded those of controls by, on average, 25% at diastole and 22% at systole. Our observations are consistent with hemodynamic outcomes attained in other rodent models of chronic cigarette smoking (13,30,36,37) and recapitulate occurrences in chronic smokers, as follows. After correcting for antihypertensive treatment, Tomiyama et al (38) found that former smokers, quitters, and heavy smokers experienced higher systolic blood pressure compared with never and moderate smokers in a large cohort study.…”

Electronic Cigarette Use and the Risk of Cardiovascular Diseases

“…Ex vivo experiments of wire tension myography and force transduction showed an increased thoracic aortic tension in response to vasoactive-inducing compounds in mice chronically exposed to e-cigarettes ( 147 ). In animal models, mice were exposed for 60 weeks to the e-cigarette with a concentration of nicotine from 0 to 24 mg/mL showed endothelial dysfunction and an increase in endothelial ROS, in addition to a thickening of the vessel wall were dependent on nicotine concentration ( 186 ). Experiments in mice showed that e-cigarettes produced uncoupling of eNOS, and peroxynitrite formation may lead to vascular endothelial dysfunction ( 187 ).…”

Fundamentals of vaping-associated pulmonary injury leading to severe respiratory distress

“…Observation of in vitro system is advantageous for several reasons including simplifying, focusing, and increasing throughput with targeted analyses of select cell or tissue types, but extrapolating findings to the in vivo setting remain problematic without corresponding animal studies. Experimentation conducted using animal models shows varying outcomes after vape juice exposure ranging from negligible to substantial ( 24 , 32 , 33 , 34 ). Inconsistent findings are undoubtedly due, at least in part, to variability in exposure protocols.…”