TitleAerosolized vitamin E acetate causes oxidative injury in mice and in alveolar macrophages.
Publication TypeJournal Article
Year of Publication2022
AuthorsMatsumoto S, Traber MG, Leonard SW, Choi J, Fang X, Maishan M, Wick KD, Jones KD, Calfee CS, Gotts JE, Matthay MA
JournalAm J Physiol Lung Cell Mol Physiol
Date Published2022 Jun 01
KeywordsAcetates, Animals, Electronic Nicotine Delivery Systems, Humans, Inflammation, Influenza, Human, Lung Injury, Macrophages, Alveolar, Mice, Oxidative Stress, Vaping, Vitamin E

Although vitamin E acetate (VEA) is suspected to play a causal role in the development of electronic-cigarette, or vaping, product use-associated lung injury (EVALI), the underlying biological mechanisms of pulmonary injury are yet to be determined. In addition, no study has replicated the systemic inflammation observed in humans in a murine EVALI model, nor investigated potential additive toxicity of viral infection in the setting of exposure to vaping products. To identify the mechanisms driving VEA-related lung injury and test the hypothesis that viral infection causes additive lung injury in the presence of aerosolized VEA, we exposed mice to aerosolized VEA for extended times, followed by influenza infection in some experiments. We used mass spectrometry to evaluate the composition of aerosolized VEA condensate and the VEA deposition in murine or human alveolar macrophages. Extended vaping for 28 days versus 15 days did not worsen lung injury but caused systemic inflammation in the murine EVALI model. Vaping plus influenza increased lung water compared with virus alone. Murine alveolar macrophages exposed to vaped VEA hydrolyzed the VEA to vitamin E with evidence of oxidative stress in the alveolar space and systemic circulation. Aerosolized VEA also induced cell death and chemokine release and reduced efferocytotic function in human alveolar macrophages in vitro. These findings provide new insights into the biological mechanisms of VEA toxicity.

Alternate JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID35318859
PubMed Central IDPMC9109788
Grant ListP30 DK063720 / DK / NIDDK NIH HHS / United States
R01 HL134828 / HL / NHLBI NIH HHS / United States
U54 HL147127 / HL / NHLBI NIH HHS / United States