双硫死亡在心血管疾病中的研究进展： 分子机制、潜在作用及转化意义

Advances in Research on Disulfidptosis in Cardiovascular Diseases: Molecular Mechanisms, Potential Roles, and Translational Significance

摘要: 双硫死亡(disulfidptosis)是一种由异常二硫键应激驱动的调节性细胞死亡方式，其发生依赖于SLC7A11高表达与葡萄糖缺乏共同作用。在此条件下，细胞内的NADPH生成不足，导致胱氨酸还原受阻并异常积聚，进而诱发细胞骨架蛋白的异常二硫键交联，最终导致细胞骨架崩塌和细胞死亡。与凋亡、铁死亡等传统细胞死亡方式相比，双硫死亡在触发条件、执行靶点及干预策略等方面具有显著独特性。近年来的研究表明，双硫死亡与心肌缺血–再灌注损伤、心肌梗死及心肌肥厚等心血管疾病的代谢失衡、氧化应激及细胞骨架损伤等病理过程具有潜在关联。本文系统综述了双硫死亡的核心分子机制，并与其他已知细胞死亡方式进行了比较，重点探讨了其在心血管疾病中的潜在作用及研究进展，并对双硫死亡相关候选生物标志物及干预策略的转化前景进行了展望。

Abstract: Disulfidptosis is a form of regulated cell death driven by aberrant disulfide stress, and its occurrence depends on the combined effects of high SLC7A11 expression and glucose deprivation. Under these conditions, insufficient intracellular NADPH generation impairs the reduction of cystine, leading to its abnormal accumulation, which in turn induces aberrant disulfide crosslinking of cytoskeletal proteins and ultimately results in cytoskeletal collapse and cell death. Compared with traditional modes of cell death such as apoptosis and ferroptosis, disulfidptosis exhibits marked uniqueness in its triggering conditions, execution targets, and potential intervention strategies. Recent studies have suggested that disulfidptosis may be potentially associated with pathological processes involved in cardiovascular diseases, including metabolic imbalance, oxidative stress, and cytoskeletal injury in myocardial ischemia-reperfusion injury, myocardial infarction, and cardiac hypertrophy. This article systematically reviews the core molecular mechanisms of disulfidptosis and compares it with other known forms of cell death, with a particular focus on its potential roles and research progress in cardiovascular diseases. In addition, the translational prospects of disulfidptosis-related candidate biomarkers and therapeutic strategies are also discussed.