E-cigarette aerosol exacerbates cardiovascular oxidative stress in mice with an inactive aldehyde dehydrogenase 2 enzyme

AimsE-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. The aim of this study was to determine how e-cigarette aerosol exposure, when coupled with genetics, impacts cardiovascular oxidative stress in wild type ALDH2 and ALDH2*2 knock-in mice. Methods and ResultsUsing selective ion flow mass spectrometry, we determined that e-cigarette aerosol contains acetaldehyde that are 10-fold higher than formaldehyde or acrolein. Next, using wild type ALDH2 and ALDH2*2 knock-in rodents, we identified organ-specific differences in ALDH2 with the heart having ~1.5-fold less ALDH2 enzyme activity relative to the liver and lung. In isolated cardiac myocytes, acetaldehyde exposure (30 seconds, 0.1-1 M) caused a 4-fold greater peak in calcium levels for ALDH2*2 relative to ALDH2 cardiomyocytes. ALDH2*2 cardiomyocytes exposed to acetaldehyde also demonstrated a 2-fold increase in ROS production and 2.5-fold increase in 4HNE protein adducts relative to ALDH2 cardiomyocytes. For intact rodents, ALDH2*2 knock-in mice exposed to e-cigarette aerosol had an increased heart rate beginning 5 days after exposure compared to wild type ALDH2 mice (775{+/-}30 bpm versus 679{+/-}33 bpm, respectively, *p View larger version (50K): org.highwire.dtl.DTLVardef@cbba2borg.highwire.dtl.DTLVardef@12b8470org.highwire.dtl.DTLVardef@3ffb8org.highwire.dtl.DTLVardef@89b10b_HPS_FORMAT_FIGEXP M_FIG C_FIG E-cigarette aerosol exposure triggers increases in ROS that lead to increased protein carbonylation, MDA production, and elevates phosphorylated NF-kB. This exposure to e-cigarette aerosol leads to increases in cardiovascular oxidative stress. For the ALDH2*2 variant, there is limited ability to metabolize the reactive aldehydes from e-cigarette aerosol and with increased levels of oxidative stress at baseline relative to wild type ALDH2, e-cigarette aerosol increased oxidative stress, protein carbonylation, and phosphorylation of NF-kB relative to wild type ALDH2 rodents.