Institute of Cardiovascular Sciences, Saint Boniface Hospital, and Departments of Physiology and Pathophysiology, University of Manitoba , Winnipeg , Canada.
Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba , Winnipeg , Canada.
Am J Physiol Heart Circ Physiol. 2019 Jul 1;317(1):H156-H163. doi: 10.1152/ajpheart.00076.2019. Epub 2019 May 3.
Cell death is an important component of the pathophysiology of any disease. Myocardial disease is no exception. Understanding how and why cells die, particularly in the heart where cardiomyocyte regeneration is limited at best, becomes a critical area of study. Ferroptosis is a recently described form of nonapoptotic cell death. It is an iron-mediated form of cell death that occurs because of accumulation of lipid peroxidation products. Reactive oxygen species and iron-mediated phospholipid peroxidation is a hallmark of ferroptosis. To date, ferroptosis has been shown to be involved in cell death associated with Alzheimer's disease, Huntington's disease, cancer, Parkinson's disease, and kidney degradation. Myocardial reperfusion injury is characterized by iron deposition as well as reactive oxygen species production. These conditions, therefore, favor the induction of ferroptosis. Currently there is no available treatment for reperfusion injury, which accounts for up to 50% of the final infarct size. This review will summarize the evidence that ferroptosis can induce cardiomyocyte death following reperfusion injury and the potential for this knowledge to open new therapeutic approaches for myocardial ischemia-reperfusion injury.
细胞死亡是任何疾病病理生理学的重要组成部分。心肌疾病也不例外。了解细胞死亡的方式和原因，特别是在心肌细胞再生能力有限的心脏中，成为一个关键的研究领域。铁死亡是一种新近描述的非凋亡性细胞死亡形式。它是一种由于脂质过氧化产物积累而发生的铁介导的细胞死亡形式。活性氧和铁介导的磷脂过氧化是铁死亡的标志。迄今为止，铁死亡已被证明与阿尔茨海默病、亨廷顿病、癌症、帕金森病和肾脏退化相关的细胞死亡有关。心肌再灌注损伤的特征是铁沉积和活性氧的产生。因此，这些条件有利于诱导铁死亡。目前，尚无针对再灌注损伤的有效治疗方法，而再灌注损伤占最终梗死面积的 50%。本综述将总结铁死亡可诱导再灌注损伤后心肌细胞死亡的证据，以及这一知识为心肌缺血再灌注损伤开辟新的治疗方法的潜力。
