Short‐term e‐cigarette vapor exposure causes vascular oxidative stress and dysfunction ‐ evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX‐2)
Authors: Kuntic Marin , Oelze Matthias , Steven Sebastian , Kröller-Schön Swenja , Stamm Paul , Kalinovic Sanela , Frenis Katie , Vujacic-Mirski Ksenija , Jimenez Maria Teresa Bayo , Kvandova Miroslava , Filippou Konstantina , Al Zuabi Ahmad , Brückl Vivienne , Hahad Omar , Daub Steffen , Varveri Franco , Gori Tommaso , Huesmann Regina , Hoffmann Thorsten , Schmidt Frank P. , Keaney John F. , Daiber Andreas , Münzel Thomas 
Published: April 2020

Background

Electronic (e)‐cigarettes have been marketed as a “healthy” alternative to traditional combustible cigarettes and as an effective method of smoking cessation. There are, however, a paucity of data to support these claims. In fact, e‐cigarettes are implicated in endothelial dysfunction and oxidative stress in the vasculature and the lungs. The mechanisms underlying these side effects remain unclear. Here, we investigated the effects of e‐cigarette vapor on vascular function in smokers and experimental animals to determine the underlying mechanisms.

Methods and Results

Acute e‐cigarette smoking produced a marked impairment of endothelial function in chronic smokers determined by flow‐mediated dilation. In mice, e‐cigarette vapor without nicotine had more detrimental effects on endothelial function, markers of oxidative stress, inflammation and lipid peroxidation than vapor containing nicotine. These effects of e‐cigarette vapor were largely absent in mice lacking phagocytic NADPH oxidase (NOX‐2) or upon treatment with the endothelin receptor blocker macitentan or the FOXO3 activator bepridil. We also established that the e‐cigarette product acrolein, a reactive aldehyde, recapitulated many of the NOX‐2‐dependent effects of e‐cigarette vapor using in vitro blood vessel incubation.

Conclusions

E‐cigarette vapor exposure increases vascular, cerebral and pulmonary oxidative stress via a NOX‐2‐dependent mechanism. Our study identifies the toxic aldehyde acrolein as a key mediator of the observed adverse vascular consequences. Thus, e‐cigarettes have the potential to induce marked adverse cardiovascular, pulmonary and cerebrovascular consequences. Since e‐cigarette use is increasing, particularly amongst youth, our data suggest that aggressive steps are warranted to limit the health risks of e‐cigarettes.

Support or Funding Information

The present work was supported by a vascular biology research grant from the Foundation Heart of Mainz and by a vascular biology research grant from the Boehringer Ingelheim Foundation for the collaborative research group „Novel and neglected cardiovascular risk factors: molecular mechanisms and therapeutic implications" to study the effects of environmental risk factors on vascular function and oxidative stress. R. H. holds a PhD stipend of the Max Planck Graduate Center with the Johannes Gutenberg University Mainz. T.M. is PI of the DZHK (German Center for Cardiovascular Research), Partner Site Rhine‐Main, Mainz, Germany.

Central scheme: Proposed mechanisms of E‐cigarette mediated cerebro/cardiovascular complications from studies in mice.

The described adverse effects are also operative in the disease development and progression of classical cerebro/cardiovascular disease such as stroke, atherosclerosis, hypertension and coronary artery disease. Light blue color items represent pharmacological/genetic interventions.

Figure 1