铁死亡与心血管疾病的关系及其靶向治疗

Relationship between Ferroptosis and Cardiovascular Disease and Its Targeted Therapy

铁死亡是一种以细胞内铁过载及脂质代谢异常为特征的程序性细胞死亡方式。关于铁死亡,除了铁代谢、脂质代谢、氧化-抗氧化失调等经典机制外,近年来研究发现,铁蛋白自噬、脂肪自噬、线粒体代谢障碍、核因子E2相关因子2(Nrf2)基因调控、内体分拣转运复合体Ⅲ(ESCRT-Ⅲ)介导的膜修复机制等也参与调控铁死亡;同时,铁死亡参与多种心血管疾病的发生。本文综述了铁死亡相关机制研究进展,分析了其与心肌缺血再灌注损伤、阿霉素的心肌毒性、心力衰竭、动脉粥样硬化和主动脉瓣膜钙化等心血管疾病的关系,并对其靶向治疗相关研究进行总结分析,指出铁死亡有望成为心血管疾病的重要干预靶点,可为心血管疾病的相关药物研究提供参考。

Ferroptosis is a programmed cell death pattern characterized by intracellular iron overload and abnormal lipid metabolism.Regarding ferroptosis,in addition to classic mechanisms such as iron metabolism,lipid metabolism,and oxidative antioxidant imbalance,recent studies have found that ferritin autophagy,fat autophagy,mitochondrial metabolic disorders,nuclear factor erythroid 2-related factor 2(Nrf2)gene regulation,and the membrane repair mechanism mediated by endosomal sorting complex required for transportⅢ(ESCRT-Ⅲ)are also involved in regulating ferroptosis.At the same time,ferroptosis is involved in the development of multiple cardiovascular diseases.In this paper,we reviewed the research progress on the mechanism of ferroptosis,analyzed its relationship with myocardial ischemia-reperfusion injury,myocardial toxicity of adriamycin,heart failure,atherosclerosis,aortic valve calcification and other cardiovascular diseases,and summarized and analyzed relevant studies on its targeted therapy,indicating that ferroptosis is expected to become an important intervention target for cardiovascular diseases.This can provide reference for drug research of cardiovascular diseases.