ALDH2 polymorphism and myocardial infarction: From alcohol metabolism to redox regulation.

Autor: Lamb RJ; Institute of Cardiovascular Sciences, The Medical School, University of Birmingham, United Kingdom., Griffiths K; Institute of Cardiovascular Sciences, The Medical School, University of Birmingham, United Kingdom., Lip GYH; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Danish Centre for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark., Sorokin V; Department of Cardiac, Thoracic, and Vascular Surgery, National University Heart Centre, National University Health System, Singapore., Frenneaux MP; Academic Health System, Hamad Medical Corporation, Doha, Qatar., Feelisch M; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and NIHR Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom., Madhani M; Institute of Cardiovascular Sciences, The Medical School, University of Birmingham, United Kingdom. Electronic address: m.madhani@bham.ac.uk.
Jazyk: angličtina
Zdroj: Pharmacology & therapeutics [Pharmacol Ther] 2024 Jul; Vol. 259, pp. 108666. Date of Electronic Publication: 2024 May 17.
DOI: 10.1016/j.pharmthera.2024.108666
Abstrakt: Acute myocardial infarction (AMI) remains a leading cause of death worldwide. Increased formation of reactive oxygen species (ROS) during the early reperfusion phase is thought to trigger lipid peroxidation and disrupt redox homeostasis, leading to myocardial injury. Whilst the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) is chiefly recognised for its central role in ethanol metabolism, substantial experimental evidence suggests an additional cardioprotective role for ALDH2 independent of alcohol intake, which mitigates myocardial injury by detoxifying breakdown products of lipid peroxidation including the reactive aldehydes, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Epidemiological evidence suggests that an ALDH2 mutant variant with reduced activity that is highly prevalent in the East Asian population increases AMI risk. Additional studies have uncovered a strong association between coronary heart disease and this ALDH2 mutant variant. It appears this enzyme polymorphism (in particular, in ALDH2*2/2 carriers) has the potential to have wide-ranging effects on thiol reactivity, redox tone and therefore numerous redox-related signaling processes, resilience of the heart to cope with lifestyle-related and environmental stressors, and the ability of the whole body to achieve redox balance. In this review, we summarize the journey of ALDH2 from a mitochondrial reductase linked to alcohol metabolism, via pre-clinical studies aimed at stimulating ALDH2 activity to reduce myocardial injury to clinical evidence for its protective role in the heart.
Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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