铁死亡在心力衰竭疾病中的研究进展
The Research Progress of Ferroptosis in Heart Failure Disease
DOI: 10.12677/ACM.2023.133640, PDF,    科研立项经费支持
作者: 王袆琪：青海大学研究生院，青海 西宁；苏晓灵*：青海省人民医院心血管内科，青海 西宁
关键词: 铁死亡；心力衰竭；氧化应激；铁过载；Ferroptosis； Heart Failure； Oxidative Stress； Iron Overload
摘要: 铁死亡是一种新发现的铁离子依赖，以脂质活性氧簇累积为主要标志的全新程序性细胞死亡方式，并且其形态特点和生化特性均不同于凋亡、坏死等其他细胞死亡途径，但其作用的具体机制及药物靶点等仍尚不明确。其似乎有助于许多疾病的发展，除了与肿瘤的发展、老年化疾病、神经退行性疾病、代谢性疾病等发生发展密切相关外，在心力衰竭、心肌病、冠状动脉粥样硬化等多种疾病过程都有相应参与。本文系统介绍铁死亡及其机制，以及铁死亡在心力衰竭疾病中各种病理机制进行简要综述，以提高对铁死亡作为心力衰竭疾病治疗新靶点的认识，以期为心脏疾病的治疗提供新思路。
Abstract: Ferroptosis is a new way of programmed cell death, which is iron-dependent and marked by the accumulation of lipid reactive oxygen clusters, and its morphological characteristics and biochemi-cal characteristics are different from other cell death pathways such as apoptosis and necrosis, but the specific mechanisms and drug targets of their effects are still unclear. It seems to contribute to the development of many diseases, in addition to the development of tumor, aging diseases, neuro-degenerative diseases, metabolic diseases and other closely related to the occurrence and devel-opment of heart failure, cardiomyopathy, coronary atherosclerosis and other disease processes have been involved. In this paper, ferroptosis and its mechanism are systematically introduced, and various pathological mechanisms of ferroptosis in heart failure are briefly reviewed, in order to im-prove the understanding of ferroptosis as a new target for the treatment of heart failure and pro-vide new ideas for the treatment of heart disease.
文章引用：王袆琪, 苏晓灵. 铁死亡在心力衰竭疾病中的研究进展[J]. 临床医学进展, 2023, 13(3): 4459-4465. https://doi.org/10.12677/ACM.2023.133640

参考文献

[1] Dixon, S.J., Lemberg, K.M., Lamprecht, M.R., et al. (2012) Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death. Cell, 149, 1060-1072. [Google Scholar] [CrossRef] [PubMed]
[2] Hirschhorn, T. and Stockwell, B.R. (2019) The Development of the Concept of Ferroptosis. Free Radical Biology & Medicine, 133, 130-143. [Google Scholar] [CrossRef] [PubMed]
[3] Yang, W.S., SriRamaratnam, R., Welsch, M.E., et al. (2014) Regulation of Ferroptotic Cancer Cell Death by GPX4. Cell, 156, 317-331. [Google Scholar] [CrossRef] [PubMed]
[4] Fuchs, Y. and Steller, H. (2011) Programmed Cell Death in Animal Development and Disease. Cell, 147, 742-758. [Google Scholar] [CrossRef] [PubMed]
[5] Yu, H., Guo, P., Xie, X., et al. (2017) Ferroptosis, a New Form of Cell Death, and Its Relationships with Tumourous Diseases. Journal of Cellular and Molecular Medicine, 21, 648-657. [Google Scholar] [CrossRef] [PubMed]
[6] Hao, S., Liang, B., Huang, Q., et al. (2018) Metabolic Networks in Fer-roptosis. Oncology Letters, 15, 5405-5411. [Google Scholar] [CrossRef] [PubMed]
[7] DeHart, D.N., Fang, D., Heslop, K., et al. (2018) Opening of Voltage Dependent Anion Channels Promotes Reactive Oxygen Species Generation, Mitochondrial Dysfunction and Cell Death in Cancer Cells. Biochemical Pharmacology, 148, 155-162. [Google Scholar] [CrossRef] [PubMed]
[8] Stockwell, B.R., Friedmann Angeli, J.P., Bayir, H., et al. (2017) Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell, 171, 273-285. [Google Scholar] [CrossRef] [PubMed]
[9] Stoyanovsky, D.A., Tyurina, Y.Y., Shrivastava, I., et al. (2019) Iron Catalysis of Lipid Peroxidation in Ferroptosis: Regulated Enzymatic or Random Free Radical Reaction? Free Radical Biology & Medicine, 133, 153-161. [Google Scholar] [CrossRef] [PubMed]
[10] Xie, Y., Hou, W., Song, X., et al. (2016) Ferroptosis: Process and Function. Cell Death and Differentiation, 23, 369-379. [Google Scholar] [CrossRef] [PubMed]
[11] Jiang, X., Stockwell, B.R. and Conrad, M. (2021) Ferroptosis: Mecha-nisms, Biology and Role in Disease. Nature Reviews. Molecular Cell Biology, 22, 266-282. [Google Scholar] [CrossRef] [PubMed]
[12] Xu, T., Ding, W., Ji, X., et al. (2019) Molecular Mechanisms of Ferroptosis and Its Role in Cancer Therapy. Journal of Cellular and Molecular Medicine, 23, 4900-4912. [Google Scholar] [CrossRef] [PubMed]
[13] Huang, C., Santofimia-Castaño, P., Liu, X., et al. (2021) NUPR1 Inhibi-tor ZZW-115 Induces Ferroptosis in a Mitochondria-Dependent Manner. Cell Death Discovery, 7, 269. [Google Scholar] [CrossRef] [PubMed]
[14] Wunderer, F., Traeger, L., Sigurslid, H.H., et al. (2020) The Role of Hepcidin and Iron Homeostasis in Atherosclerosis. Pharmacological Research, 153, Article ID: 104664. [Google Scholar] [CrossRef] [PubMed]
[15] Anderson, G.J., Frazer, D.M. and McLaren, G.D. (2009) Iron Absorption and Metabolism. Current Opinion in Gastroenterology, 25, 129-135. [Google Scholar] [CrossRef] 
[16] Kerins, M.J. and Ooi, A. (2018) The Roles of NRF2 in Modulating Cellular Iron Homeostasis. Antioxidants & Redox Signaling, 29, 1756-1773. [Google Scholar] [CrossRef] [PubMed]
[17] Yang, W.S. and Stockwell, B.R. (2016) Ferroptosis: Death by Lipid Peroxidation. Trends in Cell Biology, 26, 165-176. [Google Scholar] [CrossRef] [PubMed]
[18] Doll, S. and Conrad, M. (2017) Iron and Ferroptosis: A Still Ill-Defined Liaison. IUBMB Life, 69, 423-434. [Google Scholar] [CrossRef] [PubMed]
[19] Dowdle, W.E., Nyfeler, B., Nagel, J., et al. (2014) Selective VPS34 Inhibitor Blocks Autophagy and Uncovers a Role for NCOA4 in Ferritin Degradation and Iron Homeostasis in Vivo. Nature Cell Biology, 16, 1069-1079. [Google Scholar] [CrossRef] [PubMed]
[20] Liu, M.R., Zhu, W.T. and Pei, D.S. (2021) System Xc: A Key Regulatory Target of Ferroptosis in Cancer. Investigational New Drugs, 39, 1123-1131. [Google Scholar] [CrossRef] [PubMed]
[21] Bridges, R., Lutgen, V., Lobner, D. and Baker, D.A. (2012) Thinking outside the Cleft to Understand Synaptic Activity: Contribution of the Cystine-Glutamate Antiporter (System xc-) to Normal and Pathological Glutamatergic Signaling. Pharmacological Reviews, 64, 780-802. [Google Scholar] [CrossRef] [PubMed]
[22] Li, C., Deng, X., Xie, X., et al. (2018) Activation of Glutathione Pe-roxidase 4 as a Novel Anti-Inflammatory Strategy. Frontiers in Pharmacology, 9, 1120. [Google Scholar] [CrossRef] [PubMed]
[23] Proneth, B. and Conrad, M. (2019) Ferroptosis and Necroinflamma-tion, a Yet Poorly Explored Link. Cell Death and Differentiation, 26, 14-24. [Google Scholar] [CrossRef] [PubMed]
[24] Chen, X., Xu, S., Zhao, C. and Liu, B. (2019) Role of TLR4/NADPH Oxidase 4 Pathway in Promoting Cell Death through Autophagy and Ferroptosis during Heart Failure. Biochemical and Biophysical Research Communications, 516, 37-43. [Google Scholar] [CrossRef] [PubMed]
[25] 王华, 梁延春. 中国心力衰竭诊断和治疗指南2018 [J]. 中华心血管病杂志, 2018, 46(10): 760-789.
[26] Mosterd, A. and Hoes, A.W. (2007) Clinical Epidemiology of Heart Fail-ure. Heart (British Cardiac Society), 93, 1137-1146. [Google Scholar] [CrossRef] [PubMed]
[27] Moe, G.W. and Marín-García, J. (2016) Role of Cell Death in the Progression of Heart Failure. Heart Failure Reviews, 21, 157-167. [Google Scholar] [CrossRef] [PubMed]
[28] 胡盛寿, 高润霖, 刘力生, 朱曼璐, 王文, 王拥军, 吴兆苏, 李惠君, 顾东风, 杨跃进, 郑哲, 陈伟伟. 《中国心血管病报告2018》概要[J]. 中国循环杂志, 2019, 34(3): 209-220.
[29] 方学贤, 蔡昭贤, 王浩, 闵军霞, 王福俤. 铁过载及铁死亡在心脏疾病中的研究进展[J]. 科学通报, 2019, 64(Z2): 2974-2987.
[30] Liu, B., Zhao, C., Li, H., et al. (2018) Puerarin Protects against Heart Failure Induced by Pressure Overload through Mitigation of Ferroptosis. Biochemical and Biophysical Research Communications, 497, 233-240. [Google Scholar] [CrossRef] [PubMed]
[31] Bulluck, H., Rosmini, S., Abdel-Gadir, A., et al. (2016) Residual Myocardial Iron Following Intramyocardial Hemorrhage during the Convalescent Phase of Reperfused ST-Segment-Elevation Myocardial Infarction and Adverse Left Ventricular Remodeling. Circulation: Cardiovascular Imaging, 9, e004940. [Google Scholar] [CrossRef] 
[32] Berdoukas, V., Coates, T.D. and Cabantchik, Z.I. (2015) Iron and Oxidative Stress in Cardiomyopathy in Thalassemia. Free Radical Biology & Medicine, 88, 3-9. [Google Scholar] [CrossRef] [PubMed]
[33] Fang, X., Wang, H., Han, D., et al. (2019) Ferroptosis as a Target for Protection against Cardiomyopathy. Proceedings of the National Academy of Sciences of the United States of America, 116, 2672-2680. [Google Scholar] [CrossRef] [PubMed]
[34] Yu, H., Yang, C., Jian, L., et al. (2019) Sulfasalazine-Induced Fer-roptosis in Breast Cancer Cells Is Reduced by the Inhibitory Effect of Estrogen Receptor on the Transferrin Receptor. Oncology Reports, 42, 826-838. [Google Scholar] [CrossRef] [PubMed]
[35] Li, S. and Huang, Y. (2022) Ferroptosis: An Iron-Dependent Cell Death form Linking Metabolism, Diseases, Immune Cell and Targeted Therapy. Clinical & Translational Oncology: Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 24, 1-12. [Google Scholar] [CrossRef] [PubMed]
[36] Schubert, J., Lindahl, B., Melhus, H., et al. (2021) Low-Density Lipoprotein Cholesterol Reduction and Statin Intensity in Myocardial Infarction Patients and Major Adverse Outcomes: A Swedish Nationwide Cohort Study. European Heart Journal, 42, 243-252. [Google Scholar] [CrossRef] [PubMed]
[37] Katsiki, N., Doumas, M. and Mikhailidis, D.P. (2016) Lipids, Statins and Heart Failure: An Update. Current Pharmaceutical Design, 22, 4796-4806. [Google Scholar] [CrossRef] [PubMed]
[38] Ning, D., Yang, X., Wang, T., et al. (2021) Atorvas-tatin Treatment Ameliorates Cardiac Function and Remodeling Induced by Isoproterenol Attack through Mitigation of Ferroptosis. Biochemical and Biophysical Research Communications, 574, 39-47. [Google Scholar] [CrossRef] [PubMed]
[39] Li, N., Wang, W., Zhou, H., et al. (2020) Ferritinophagy-Mediated Ferroptosis Is Involved in Sepsis-Induced Cardiac Injury. Free Radical Biology & Medicine, 160, 303-318. [Google Scholar] [CrossRef] [PubMed]

为你推荐