铁死亡在血管内皮损伤机制中的研究进展

Research progress of ferroptosis in the pathogenesis of vascular endothelial injury

铁死亡是近几年发现的一种新的可调控的细胞死亡方式,核心是依赖于铁离子的脂质过氧化物堆积,最初的机制主要集中在溶质载体家族7成员11(SLC7A11)-谷胱甘肽(GSH)-谷胱甘肽过氧化物酶4(GPX4)途径,但后续研究发现,细胞内还存在不依赖于GPX4的途径。同时铁死亡是一种广泛存在的细胞死亡方式,涉及氧化还原平衡、脂质代谢、铁稳态以及能量代谢,与肿瘤、缺血再灌注损伤、神经退行性变等多种疾病相关。最新又有研究表明铁死亡参与了血管内皮损伤,血管内皮对于血管稳态具有重要保护作用,是动脉粥样硬化等疾病最先受累的部位,因此铁死亡有望成为保护内皮和治疗动脉粥样硬化的新靶点。这是一个十分新颖的研究方向,相关机制研究仍在不断更新和完善,本文希望通过总结铁死亡的机制进展及其在血管内皮损伤中的作用,为今后的基础研究和临床转化奠定基础。

Ferroptosis is a new type of programmed cell death discovered in recent years.The core of ferroptosis is the accumulation of lipid peroxides that depend on iron.Initially,the mechanism mainly focused on the solute carrier family 7 member 11(SLC7A11)-glutathione(GSH)-glutathione peroxidase 4(GPX4)pathway.The latest study found that there is a GPX4-independent pathway in cells,and ferroptosis is a ubiquitous form of cell death,involving redox homeostasis,lipid metabolism,iron metabolism as well as energy stress.It is related to various diseases such as tumors,ischemia-reperfusion injury,and neurodegeneration.The latest research indicated that ferroptosis is involved in vascular endothelial injury.Vascular endothelium plays an important protective role in vascular homeostasis,and is the first site to be affected by diseases such as atherosclerosis.Therefore,ferroptosis is expected to become a new target for protecting the endothelium and treating atherosclerosis.This is a very novel research direction,and the related mechanism research is still being updated and improved.This review summarizes the mechanism of ferroptosis and its role in vascular endothelial injury,laying the foundation for future basic research and clinical transformation.