Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom.
Free Radic Biol Med. 2019 Mar;133:234-237. doi: 10.1016/j.freeradbiomed.2018.08.010. Epub 2018 Aug 11.
Heart disease is a common manifestation in conditions of iron imbalance. Normal heart function requires coupling of iron supply for oxidative phosphorylation and redox signalling with tight control of intracellular iron to below levels at which excessive ROS are generated. Iron supply to the heart is dependent on systemic iron availability which is controlled by the systemic hepcidin/ferroportin axis. Intracellular iron in cardiomyocytes is controlled in part by the iron regulatory proteins IRP1/2. This mini-review summarises current understanding of how cardiac cells regulate intracellular iron levels, and of the mechanisms linking cardiac dysfunction with iron imbalance. It also highlights a newly-recognised mechanism of intracellular iron homeostasis in cardiomyocytes, based on a cell-autonomous cardiac hepcidin/ferroportin axis. This new understanding raises pertinent questions on the interplay between systemic and local iron control in the context of heart disease, and the effects on heart function of therapies targeting the systemic hepcidin/ferroportin axis.
心脏病是铁失衡状态下的一种常见表现。正常的心脏功能需要将铁供应与氧化磷酸化和氧化还原信号偶联，同时严格控制细胞内铁的含量，使其低于生成过多 ROS 的水平。心脏的铁供应取决于全身铁的可用性，而全身铁的可用性则由系统铁调素/亚铁转运蛋白轴控制。心肌细胞中的细胞内铁部分受铁调节蛋白 IRP1/2 控制。这篇综述总结了目前对心脏细胞如何调节细胞内铁水平的理解，以及将心脏功能障碍与铁失衡联系起来的机制。它还强调了一种新发现的心肌细胞内铁稳态机制，基于细胞自主的心脏铁调素/亚铁转运蛋白轴。这种新的认识提出了一些相关问题，即在心脏病的背景下，全身和局部铁控制之间的相互作用，以及针对全身铁调素/亚铁转运蛋白轴的治疗方法对心脏功能的影响。
