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铁在心血管疾病中的病理作用。

Pathological Roles of Iron in Cardiovascular Disease.

机构信息

Department of Anatomy, Biochemistry & Physiology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, United States.

Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.

出版信息

Curr Drug Targets. 2018;19(9):1068-1076. doi: 10.2174/1389450119666180605112235.

Abstract

Iron is an essential mineral required for a variety of vital biological functions. Despite being vital for life, iron also has potentially toxic aspects. Iron has been investigated as a risk factor for coronary artery disease (CAD), however, iron's toxicity in CAD patients still remains controversial. One possible mechanism behind the toxicity of iron is "ferroptosis", a newly described form of irondependent cell death. Ferroptosis is an iron-dependent form of regulated cell death that is distinct from apoptosis, necroptosis, and other types of cell death. Ferroptosis has been reported in ischemiareperfusion (I/R) injury and several other diseases. Recently, we reported that ferroptosis is a significant form of cell death in cardiomyocytes. Moreover, myocardial hemorrhage, a major event in the pathogenesis of heart failure, could trigger the release of free iron into cardiac muscle and is an independent predictor of adverse left ventricular remodeling after myocardial infarction. Iron deposition in the heart can now be detected with advanced imaging methods, such as T2 star (T2*) cardiac magnetic resonance imaging, which can non-invasively predict iron levels in the myocardium and detect myocardial hemorrhage, thus existing technology could be used to assess myocardial iron. We will discuss the role of iron in cardiovascular diseases and especially with regard to myocardial I/R injury.

摘要

铁是一种必需的矿物质,对于各种重要的生物功能都至关重要。尽管铁对生命至关重要,但它也具有潜在的毒性。铁已被研究为冠心病(CAD)的一个风险因素,但铁在 CAD 患者中的毒性仍然存在争议。铁毒性的一个可能机制是“铁死亡”,这是一种新描述的铁依赖性细胞死亡形式。铁死亡是一种不同于细胞凋亡、坏死和其他类型细胞死亡的铁依赖性调节性细胞死亡形式。铁死亡已在缺血再灌注(I/R)损伤和其他几种疾病中得到报道。最近,我们报告称铁死亡是心肌细胞中一种重要的细胞死亡形式。此外,心力衰竭发病机制中的一个主要事件——心肌出血,可能会引发游离铁释放到心肌中,并且是心肌梗死后左心室重构不良的独立预测因子。现在可以使用先进的成像方法(如 T2*心脏磁共振成像)来检测心脏中的铁沉积,这些方法可以无创地预测心肌中的铁水平并检测心肌出血,因此现有的技术可用于评估心肌铁。我们将讨论铁在心血管疾病中的作用,特别是在心肌 I/R 损伤方面。

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