E‐cigarette vapor elevates heart rate in mice with limited reactive aldehyde metabolism
Authors: Sinharoy Pritam , McAllister Stacy , Gross Eric Richard 
Published: June 2021

BackgroundE‐cigarettes contain high levels of reactive aldehydes including acrolein, acetaldehyde and formaldehyde in addition to nicotine. However, the cardiovascular effects of e‐cigarette exposure are not well studied. Furthermore, ~560 million people of East Asian descent cannot efficiently metabolize these aldehydes in e‐cigarettes due to a genetic variant in aldehyde dehydrogenase 2, known as ALDH2*2. Therefore, we tested our hypothesis that e‐cigarette vapor exposure alters heart rates in wild type ALDH2 mice and these effects are exacerbated in ALDH2*2 knock‐in mice.MethodsTo test our hypothesis, both male and female wild type and homozygote ALDH2*2 mice (8–12 weeks old) were implanted with a mouse Biopotential Telemeter (Millar) and heart rate was acquired with LabChart 8 (AD Instruments) (n = 4/genotype). All mice were exposed to 60 puffs (5 sec duration and 60 ml puff volume) a day for 5 days. With each e‐cigarette exposure, we also monitored the reactive aldehyde levels in e‐cigarette vapor in real‐time by selective ion flow mass spectrometry. Furthermore, ALDH2 expression and activity in whole heart mitochondrial fractions were determined by biochemical assays (n= 3/genotype). Statistical analysis was performed using Graph Pad Prism 6.0. Data are expressed as mean ± SEM. Student's t‐test was used for comparison between two groups and ANOVA followed by Bonferroni correction was used for multiple variant comparisons (* indicating P value <0.001).ResultsWhen compared to baseline heart rates for wild type and ALDH2*2 mice, e‐cigarette vapor exposure leads to a substantial drop in heart rate for both wild type (739 ± 6 vs. 502 ± 36* bpm, respectively) and ALDH2*2 mice (712 ± 5 vs. 500 ± 43* bpm, respectively). Additionally, 5 days of continuous e‐cigarette exposure increased the resting heart rate by 49 ± 9* bpm in wild type and 163 ± 9* bpm in ALDH2*2 mice respectively. Quantification of reactive aldehyde levels in e‐cigarettes revealed that e‐cigarette vapor contained high levels of acetaldehyde (1506 ± 179.1* ppb), acrolein (38.2 ± 4.7* ppb) and formaldehyde (52.7 ± 3.7* ppb) in contrast to ambient air (acetaldehyde 35.5 ± 4.6 ppb, acrolein 8.5 ± 1.3 ppb, and formaldehyde 7.1 ± 0.3 ppb). Furthermore, compared to wild type mice, both heart ALDH2 expression (1.3 ± 0.2 vs. 0.5 ± 0.04* ADU) and activity (3 ± 0.2 vs. 1.1 ± 0.07* μmol/min/mg) were markedly lower in ALDH2*2 mice.ConclusionTogether, these findings suggest that e‐cigarette vapor exposure triggers changes in heart rate that is more pronounced in ALDH2*2 mice. Moreover, e‐cigarettes contain reactive aldehydes, including high levels of acetaldehyde. Therefore, e‐cigarette smoking/exposure may increase the risk of developing cardiovascular disease in individuals with ALDH2*2 variant.Support or Funding InformationTobacco‐Related Disease Research Program, California, United States.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.