Premium
Acetaldehyde in e‐cigarette aerosol and cigarette smoke exacerbate pulmonary microvascular endothelial dysfunction in ALDH2*2 mice
Author(s) -
Yu Xuan,
Gross Eric
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03866
Subject(s) - aldh2 , acetaldehyde , endothelial dysfunction , chemistry , aldehyde dehydrogenase , endothelial stem cell , endothelium , endocrinology , medicine , biochemistry , ethanol , enzyme , in vitro
Background Pulmonary endothelial dysfunction caused by the frequent exposure to cigarette smoke can lead to pulmonary artery hypertension (PAH). E‐cigarette vapor, similar to cigarette smoke, contains the aldehydes including acetaldehyde. Further, ~560 million people carry an inactivating genetic variant in aldehyde dehydrogenase 2 (ALDH2), known as ALDH2*2, the primary enzyme responsible for metabolizing acetaldehyde. However, little is known how reactive acetaldehyde present in cigarette smoke and e‐cigarette aerosol, when coupled with genetics, influence pulmonary vascular function. Hypothesis: Acetaldehyde in e‐cigarette aerosol and cigarette smoke lead to pulmonary endothelial dysfunction that is exacerbated in mice carrying the ALDH2*2 variant. Methods: Primary cultures of pulmonary microvascular endothelial cells from wild type ALDH2 and ALDH2*2 male mice were used. Cultures were treated with acetaldehyde (1 μM for 1 hour) in the presence and absence of the ALDH2 activator, Alda‐1 (20 μM). Intracellular ROS accumulation, reactive aldehyde‐induced protein adducts, mitochondrial bioenergetics, and endothelial function by capillary tube formation were measured. ANOVA with Bonferroni correction was performed for multiple comparisons between groups. * P <0.05. Results: In ALDH2 and ALDH2*2 mice, no differences were noted in endothelial cell morphology and expression of CD31, an endothelial specific marker. However, when exposed to acetaldehyde, pulmonary microvascular endothelial cells from ALDH2*2 mice showed a 91.2±23.2% increase in 4‐HNE‐induced protein adducts, a 27.8±5.1% reduction in mitochondrial bioenergetics, a 11.1±1.6% decrease in cell viability, and an 70.4±17.2% exacerbation of endothelial dysfunction compared to wild type ALDH2 cells ( p <0.05 for each assay, n=3 biological replicates). Pretreatment with Alda‐1 partially reversed the oxidative stress and endothelial injury caused by acetaldehyde treatment. Conclusion: Acetaldehyde, the primary aldehyde present in e‐cigarette aerosol which is also in cigarette smoke triggers pulmonary endothelial dysfunction particularly for rodents carrying an inactivating ALDH2 variant, ALDH2*2. This study provides a mechanism how e‐cigarette vapor similar to cigarette smoke can trigger endothelial dysfunction that can over time potentially lead to the development of PAH.