Wang Yuqin, Zhao Yajie, Ye Ting, Yang Liming, Shen Yanna, Li Hong
Department of Pathophysiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China.
Department of Pathophysiology, Harbin Medical University-Daqing, Daqing, China.
Front Cell Dev Biol. 2021 Dec 16;9:809457. doi: 10.3389/fcell.2021.809457. eCollection 2021.
Atherosclerosis (AS) is a major cause of cardiovascular diseases such as coronary heart disease, heart failure and stroke. Abnormal lipid metabolism, oxidative stress and inflammation are the main features of AS. Ferroptosis is an iron-driven programmed cell death characterized by lipid peroxidation, which have been proved to participate in the development and progression of AS by different signal pathways. NRF2-Keap1 pathway decreases ferroptosis associated with AS by maintaining cellular iron homeostasis, increasing the production glutathione, GPX4 and NADPH. The p53 plays different roles in ferroptosis at different stages of AS in a transcription-dependent and transcription- independent manner. The Hippo pathway is involved in progression of AS, which has been proved the activation of ferroptosis. Other transcription factors, such as ATF3, ATF4, STAT3, also involved in the occurrence of ferroptosis and AS. Certain proteins or enzymes also have a regulatory role in AS and ferroptosis. In this paper, we review the mechanism of ferroptosis and its important role in AS in an attempt to find a new relationship between ferroptosis and AS and provide new ideas for the future treatment of AS.
动脉粥样硬化(AS)是冠心病、心力衰竭和中风等心血管疾病的主要病因。脂质代谢异常、氧化应激和炎症是AS的主要特征。铁死亡是一种由铁驱动的程序性细胞死亡,其特征是脂质过氧化,已被证明通过不同信号通路参与AS的发生发展。NRF2-Keap1通路通过维持细胞铁稳态、增加谷胱甘肽、GPX4和NADPH的产生来减少与AS相关的铁死亡。p53在AS不同阶段的铁死亡中以转录依赖和非转录依赖的方式发挥不同作用。Hippo通路参与AS的进展,已被证明可激活铁死亡。其他转录因子,如ATF3、ATF4、STAT3,也参与铁死亡和AS的发生。某些蛋白质或酶在AS和铁死亡中也具有调节作用。本文综述了铁死亡的机制及其在AS中的重要作用,试图寻找铁死亡与AS之间的新关系,并为AS的未来治疗提供新思路。