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Aldehyde Dehydrogenase 2 Ameliorates Chronic Alcohol Consumption-Induced Atrial Fibrillation through Detoxification of 4-HNE.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2020 Sep 12; Vol. 21 (18). Date of Electronic Publication: 2020 Sep 12. - Publication Year :
- 2020
-
Abstract
- Aldehyde dehydrogenase 2 (ALDH2) is an enzyme that detoxifies reactive oxygen species (ROS)-generated aldehyde adducts such as 4-hydroxy-trans-2-nonenal (4-HNE). Previous meta-analyses have shown an increase in the risk of atrial fibrillation (AF) in patients with chronic alcohol consumption. ALDH2*2 , a common dysfunctional polymorphism in the ALDH2 gene, has been linked to an increased risk of cancer and heart disease. We tested the effect of ALDH2 deficiency on alcohol-induced AF in a murine model of chronic-binge ethanol feeding, with ALDH2*2 knock-in (KI) mice generated by a CRISPR/CAS9 system. In addition, right atrial appendages were obtained from eight patients with AF undergoing open heart surgery. The results showed that burst atrial pacing induced a greater susceptibility to AF in ALDH2*2 KI mice exposed to chronic ethanol intoxication than in wild-type mice, resulting from a higher degree of 4-HNE accumulation and collagen deposition in their atria. Alda-1 attenuated transforming growth factor beta 1 (TGF-β1) expression and collagen deposition in the atria and reduced AF inducibility. Patients with AF and the ALDH2*2 allele exhibited greater oxidative stress and substrate remodeling in their atria than non-carriers. In conclusion, ALDH2 deficiency may increase the risk of chronic alcohol and tachypacing-induced AF through the accumulation of 4-HNE and increased ROS production.
- Subjects :
- Alcohol Drinking genetics
Alcoholism genetics
Alcoholism metabolism
Aldehyde Dehydrogenase, Mitochondrial genetics
Alleles
Animals
Atrial Fibrillation genetics
Collagen metabolism
Female
Humans
Male
Mice
Mice, Inbred C57BL
Oxidative Stress genetics
Polymorphism, Genetic genetics
Transforming Growth Factor beta metabolism
Alcohol Drinking metabolism
Aldehyde Dehydrogenase, Mitochondrial metabolism
Aldehydes metabolism
Atrial Fibrillation metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 21
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32932651
- Full Text :
- https://doi.org/10.3390/ijms21186678