Circulation：我国学者发现，这个导致中国人喝酒脸红的基因突变，通过铁死亡加剧心肌梗死

Core Viewpoint - The study highlights the role of ALDH22 mutation in exacerbating acute heart failure post-myocardial infarction by promoting ferroptosis through selective translation of specific mRNAs [4][7]. Group 1: ALDH2 and Its Mutation - ALDH2 plays a crucial role in detoxifying lipid peroxidation products and alcohol metabolism, with the common mutation ALDH22 present in 40% of East Asian populations, leading to reduced enzyme activity and increased myocardial infarction risk [3]. - The ALDH22 mutation results in decreased ALDH2 protein levels, which disrupts its interaction with the eIF3 complex, promoting the formation of the eIF3E-eIF4G1-mRNA complex that drives the translation of ferroptosis-related genes [6][7]. Group 2: Research Findings - The research involved 177 Chinese patients with acute heart failure, comparing wild-type and ALDH22 genotypes, and established a myocardial infarction model in mice [5]. - ALDH22 carriers exhibited more severe heart failure post-acute myocardial infarction, characterized by increased bioactive lipids and decreased antioxidants in plasma, indicating ferroptosis [5]. - Inhibition of ferroptosis using Fer-1 significantly improved cardiac function in ALDH22 mouse models, reversing markers of ferroptosis [5]. Group 3: Mechanism of Ferroptosis - ALDH2 interacts with the eIF3 complex to prevent the formation of the eIF3E-eIF4G1-mRNA complex, which is disrupted by the ALDH22 mutation, leading to increased translation of mRNAs that promote ferroptosis [6]. - Continuous knockdown of eIF3E in myocardial cells can restore cardiac function in ALDH22 carriers by alleviating ferroptosis [6][7]. Group 4: Therapeutic Implications - Targeting ferroptosis presents a viable cardiac protection strategy, particularly for ALDH2*2 carriers, to mitigate myocardial injury [5][7].