Zhang Jia-Bao, Tong Jie, Sun Di-Yang, Fu Jiang-Tao, Li Dong-Jie, Wang Pei
Department of Pharmacology, College of Pharmacy, Naval Medical University/Second Military Medical University, Shanghai, China.
Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Med Res Rev. 2023 May;43(3):683-712. doi: 10.1002/med.21934. Epub 2023 Jan 19.
Cardio-metabolic-diseases (cardio-metabolic-diseases) are leading causes of death and disability worldwide and impose a tremendous burden on whole society as well as individuals. As a new type of regulated cell death (RCD), ferroptosis is distinct from several classical types of RCDs such as apoptosis and necroptosis in cell morphology, biochemistry, and genetics. The main molecular mechanisms of ferroptosis involve iron metabolism dysregulation, mitochondrial malfunction, impaired antioxidant capacity, accumulation of lipid-related peroxides and membrane disruption. Within the past few years, mounting evidence has shown that ferroptosis contributes to the pathophysiological process in cardio-metabolic-diseases. However, the exact roles and underlying molecular mechanisms have not been fully elucidated. This review comprehensively summarizes the mechanism of ferroptosis in the development and progression of cardio-metabolic-diseases, so as to provide new insights for cardio-metabolic-diseases pathophysiology. Moreover, we highlight potential druggable molecules in ferroptosis signaling pathway, and discuss recent advances in management strategies by targeting ferroptosis for prevention and treatment of cardio-metabolic-diseases.
心血管代谢疾病是全球范围内导致死亡和残疾的主要原因，给整个社会以及个人都带来了巨大负担。作为一种新型的程序性细胞死亡（RCD），铁死亡在细胞形态、生物化学和遗传学方面与凋亡和坏死性凋亡等几种经典的程序性细胞死亡类型不同。铁死亡的主要分子机制包括铁代谢失调、线粒体功能障碍、抗氧化能力受损、脂质相关过氧化物的积累和膜破坏。在过去几年中，越来越多的证据表明铁死亡参与了心血管代谢疾病的病理生理过程。然而，其确切作用和潜在分子机制尚未完全阐明。本综述全面总结了铁死亡在心血管代谢疾病发生发展过程中的机制，以期为心血管代谢疾病的病理生理学提供新的见解。此外，我们重点介绍了铁死亡信号通路中潜在的可药物化分子，并讨论了通过靶向铁死亡预防和治疗心血管代谢疾病的管理策略的最新进展。
