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Updated: Sep 6, 2025
Generation of Electronic Cigarette Aerosol by a Third-Generation Machine-Vaping Device: Application to Toxicological Studies
Published on: August 25, 2018
E-cigarette aerosol exacerbates cardiovascular oxidative stress in mice with an inactive aldehyde dehydrogenase 2
Xuan Yu1, Xiaocong Zeng1, Feng Xiao1
1Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
Background:
E-cigarette aerosol containing aldehydes, including acetaldehyde, are metabolized by the enzyme aldehyde dehydrogenase 2 (ALDH2). However, little is known how aldehyde exposure from e-cigarettes, when coupled with an inactivating ALDH2 genetic variant, ALDH2*2 (present in 8% of the world population), affects cardiovascular oxidative stress.
Objectives:
The study was to determine how e-cigarette aerosol exposure, coupled with genetics, impacts cardiovascular oxidative stress in wild type ALDH2 and ALDH2*2 knock-in mice.
Methods:
Using selective ion flow mass spectrometry, we determined e-cigarette aerosol contains acetaldehyde levels 10-fold higher than formaldehyde or acrolein. Based on this finding, we tested how isolated ALDH2*2 primary cardiomyocytes respond to acetaldehyde and how intact ALDH2*2 knock-in rodents instrumented with telemeters respond physiologically and at the molecular level to 10 days of e-cigarette aerosol exposure relative to wild type ALDH2 rodents.
Results:
For ALDH2*2 isolated cardiomyocytes, acetaldehyde (1 μM) caused a 4-fold greater peak calcium influx, 2-fold increase in ROS production and 2-fold increase in 4-HNE-induced protein adducts relative to wild-type ALDH2 cardiomyocytes. The heart rate in ALDH2*2 mice increased ∼200 beats/min, while, heart rate in ALDH2 mice increased ∼150 beats/min after 10 days of e-cigarette exposure, relative to air-exposed mice. E-cigarette aerosol exposure triggered ∼1.3 to 2-fold higher level of protein carbonylation, lipid peroxidation, and phosphorylation of NF-κB for both strains of mice, with this response exacerbated for ALDH2*2 mice.
Conclusions:
Our findings indicate people carrying an ALDH2*2 genetic variant may be more susceptible to increases in cardiovascular oxidative stress from e-cigarette aerosol exposure.
