Institute of Cardiovascular Sciences, The Medical School, University of Birmingham, United Kingdom.
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.
Pharmacol Ther. 2024 Jul;259:108666. doi: 10.1016/j.pharmthera.2024.108666. Epub 2024 May 17.
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.
急性心肌梗死（AMI）仍然是全球范围内导致死亡的主要原因。在早期再灌注阶段，活性氧（ROS）的形成增加被认为会引发脂质过氧化并破坏氧化还原平衡，导致心肌损伤。虽然线粒体酶醛脱氢酶 2（ALDH2）主要因其在乙醇代谢中的核心作用而被广泛认可，但大量实验证据表明，ALDH2 具有独立于酒精摄入的额外心脏保护作用，通过解毒脂质过氧化的分解产物，包括反应性醛，如丙二醛（MDA）和 4-羟基壬烯醛（4-HNE），从而减轻心肌损伤。流行病学证据表明，东亚人群中高度流行的活性降低的 ALDH2 突变变体增加了 AMI 风险。此外的研究揭示了冠心病与这种 ALDH2 突变变体之间存在强烈关联。似乎这种酶多态性（特别是在 ALDH2*2/2 携带者中）有可能对硫醇反应性、氧化还原调tone 以及因此对许多氧化还原相关信号过程产生广泛影响，影响心脏应对与生活方式相关和环境应激源的能力，以及全身实现氧化还原平衡的能力。在这篇综述中，我们总结了 ALDH2 的历程，从与酒精代谢相关的线粒体还原酶，通过旨在刺激 ALDH2 活性以减少心肌损伤的临床前研究，到其在心脏中的保护作用的临床证据。
