The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease.
The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease.
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心脏病中铁和铁死亡的分子和代谢景观
DOI：
10.1038/s41569-022-00735-4
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发表时间：
2023-01
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铁稳态的维持对正常的心脏功能是必不可少的。越来越多的证据表明，铁失衡是心血管疾病许多亚型的共同特征。在过去的10年中，铁依赖性细胞死亡的一种形式，已越来越被认为是介导许多心血管疾病的发病机制和进展的重要过程，包括动脉粥样硬化，药物诱导的心力衰竭，心肌缺血-再灌注损伤，败血症诱导的心肌病，心律失常和糖尿病心肌病。因此，对心肌细胞铁代谢和铁凋亡调控机制的深入了解可能会改善疾病管理。在这篇综述中，我们总结了在心血管疾病的背景下，铁信号和铁凋亡的代谢和分子途径之间的关系。我们还讨论了铁凋亡在心血管疾病治疗中的潜在靶点，并描述了这些新的治疗靶点目前的局限性和未来的发展方向。自从十年前发现铁凋亡以来，这种铁依赖性的调节性细胞死亡形式与心血管疾病的发病机制有关。在这篇综述中，Fudi Wang及其同事讨论了心血管系统背景下铁信号代谢途径与铁凋亡之间的联系，并描述了铁凋亡抑制剂在治疗心血管疾病中的潜力。终末分化心肌细胞的死亡是多种心血管疾病发展的重要致病因素。铁凋亡是一种由铁依赖性脂质过氧化驱动的调节性细胞死亡的新特征形式，与心血管疾病有关。铁蛋白缺乏症涉及多种代谢过程，包括铁、脂质和谷胱甘肽代谢。体外和体内证据均支持铁凋亡在心肌缺血-再灌注损伤、蒽环类药物介导的心脏毒性、脓毒症诱导的心脏损伤、肥厚型心肌病和糖尿病性心肌病中的病理生理作用。用特异性抑制剂靶向铁细胞增多症可能会为以前无法治疗的心血管疾病提供新的治疗机会。
The maintenance of iron homeostasis is essential for proper cardiac function. A growing body of evidence suggests that iron imbalance is the common denominator in many subtypes of cardiovascular disease. In the past 10 years, ferroptosis, an iron-dependent form of regulated cell death, has become increasingly recognized as an important process that mediates the pathogenesis and progression of numerous cardiovascular diseases, including atherosclerosis, drug-induced heart failure, myocardial ischaemia–reperfusion injury, sepsis-induced cardiomyopathy, arrhythmia and diabetic cardiomyopathy. Therefore, a thorough understanding of the mechanisms involved in the regulation of iron metabolism and ferroptosis in cardiomyocytes might lead to improvements in disease management. In this Review, we summarize the relationship between the metabolic and molecular pathways of iron signalling and ferroptosis in the context of cardiovascular disease. We also discuss the potential targets of ferroptosis in the treatment of cardiovascular disease and describe the current limitations and future directions of these novel treatment targets. Since the discovery of ferroptosis a decade ago, this iron-dependent form of regulated cell death has been implicated in the pathogenesis of cardiovascular disease. In this Review, Fudi Wang and colleagues discuss the link between the metabolic pathways of iron signalling and ferroptosis in the context of the cardiovascular system and describe the potential of ferroptosis inhibitors in the treatment of cardiovascular disease. The death of terminally differentiated cardiomyocytes is an important pathogenic contributor to the development of several forms of cardiovascular disease. Ferroptosis is a newly characterized form of regulated cell death driven by iron-dependent lipid peroxidation and linked to cardiovascular disease. Ferroptosis involves various metabolic processes, including iron, lipid and glutathione metabolism. Both in vitro and in vivo evidence supports the pathophysiological role of ferroptosis in myocardial ischaemia–reperfusion injury, anthracycline-mediated cardiotoxicity, sepsis‑induced heart injury, hypertrophic cardiomyopathy and diabetic cardiomyopathy. Targeting ferroptosis with specific inhibitors might provide new therapeutic opportunities for previously untreatable cardiovascular conditions.
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DOI：
10.1126/science.aaw9872
发表时间：
2020-04-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badgley MA;Kremer DM;Maurer HC;DelGiorno KE;Lee HJ;Purohit V;Sagalovskiy IR;Ma A;Kapilian J;Firl CEM;Decker AR;Sastra SA;Palermo CF;Andrade LR;Sajjakulnukit P;Zhang L;Tolstyka ZP;Hirschhorn T;Lamb C;Liu T;Gu W;Seeley ES;Stone E;Georgiou G;Manor U;Iuga A;Wahl GM;Stockwell BR;Lyssiotis CA;Olive KP
通讯作者：
Olive KP
影响因子：
7.4
作者：
Berdoukas, Vasilios;Coates, Thomas D.;Cabantchik, Zvi Ioav
通讯作者：
Cabantchik, Zvi Ioav
影响因子：
21.3
作者：
Friedmann Angeli JP;Schneider M;Proneth B;Tyurina YY;Tyurin VA;Hammond VJ;Herbach N;Aichler M;Walch A;Eggenhofer E;Basavarajappa D;Rådmark O;Kobayashi S;Seibt T;Beck H;Neff F;Esposito I;Wanke R;Förster H;Yefremova O;Heinrichmeyer M;Bornkamm GW;Geissler EK;Thomas SB;Stockwell BR;O'Donnell VB;Kagan VE;Schick JA;Conrad M
通讯作者：
Conrad M
影响因子：
37.8
作者：
ASCHERIO, A;WILLETT, WC;STAMPFER, MJ
通讯作者：
STAMPFER, MJ
DOI：
10.1016/j.bbamcr.2020.118881
发表时间：
2021-01
期刊：
Biochimica et biophysica acta. Molecular cell research
影响因子：
--
作者：
Chambers IG;Willoughby MM;Hamza I;Reddi AR
通讯作者：
Reddi AR