Aldehyde Dehydrogenase-2 and Atrial Fibrillation Inducibility in a Rodent Model

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Atrial fibrillation (AF) is now recognized to be the most common sustained cardiac arrhythmia and a major public health burden. Accumulating evidence suggests that there is a link between oxidative processes and AF. Many works revealed that accumulation of cytotoxic and reactive aldehydes derived from reactive oxygen species (ROS) can also severely impair cardiac functions. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that detoxifies ROS-generated aldehyde adducts. The ALDH2*2, a common polymorphism in the ALDH2 gene, results in a dramatic reduction in the enzymatic activity and has been linked to an increased risk of cancer and heart disease. Previous meta-analyses have consistently shown an increase in AF risk for chronic alcohol consumption. The mechanisms underlying the association of alcohol consumption with AF remained unclear. We hypothesize that the ALDH2*2 allele-alcohol interaction may have a role in predisposing AF. To test this hypothesis, we use a CRISPR/Cas genome-editing tool and generate an Aldh2*2 knock-in mice model. We plan to investigate whether ALDH2*2 mutation promotes AF vulnerability in chronic alcohol consumption. The results of our study may help define the role of ALDH2 in AF vulnerability and provide a useful target for therapeutic intervention in AF.

Project IDs

Project ID:PC10507-0281
External Project ID:MOST105-2314-B182-057
StatusFinished
Effective start/end date01/08/1631/07/17

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