Intravenous iron therapy results in rapid and sustained rise in myocardial iron content through a novel pathway.

IF 37.6 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS European Heart Journal Pub Date : 2024-11-08 DOI:10.1093/eurheartj/ehae359
Mayra Vera-Aviles, Syeeda Nashitha Kabir, Akshay Shah, Paolo Polzella, Dillon Yee Lim, Poppy Buckley, Charlotte Ball, Dorine Swinkels, Hanke Matlung, Colin Blans, Philip Holdship, Jeremy Nugent, Edward Anderson, Michael Desborough, Stefan Piechnik, Vanessa Ferreira, Samira Lakhal-Littleton
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Abstract

Background and aims: Intravenous iron therapies contain iron-carbohydrate complexes, designed to ensure iron becomes bioavailable via the intermediary of spleen and liver reticuloendothelial macrophages. How other tissues obtain and handle this iron remains unknown. This study addresses this question in the context of the heart.

Methods: A prospective observational study was conducted in 12 patients receiving ferric carboxymaltose (FCM) for iron deficiency. Myocardial, spleen, and liver magnetic resonance relaxation times and plasma iron markers were collected longitudinally. To examine the handling of iron taken up by the myocardium, intracellular labile iron pool (LIP) was imaged in FCM-treated mice and cells.

Results: In patients, myocardial relaxation time T1 dropped maximally 3 h post-FCM, remaining low 42 days later, while splenic T1 dropped maximally at 14 days, recovering by 42 days. In plasma, non-transferrin-bound iron (NTBI) peaked at 3 h, while ferritin peaked at 14 days. Changes in liver T1 diverged among patients. In mice, myocardial LIP rose 1 h and remained elevated 42 days after FCM. In cardiomyocytes, FCM exposure raised LIP rapidly. This was prevented by inhibitors of NTBI transporters T-type and L-type calcium channels and divalent metal transporter 1.

Conclusions: Intravenous iron therapy with FCM delivers iron to the myocardium rapidly through NTBI transporters, independently of reticuloendothelial macrophages. This iron remains labile for weeks, reflecting the myocardium's limited iron storage capacity. These findings challenge current notions of how the heart obtains iron from these therapies and highlight the potential for long-term dosing to cause cumulative iron build-up in the heart.

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静脉铁剂疗法通过一种新的途径使心肌铁含量快速、持续上升。
背景和目的:静脉注射铁剂疗法含有铁-碳水化合物复合物,旨在确保铁能通过脾脏和肝脏网状内皮巨噬细胞这一中间环节实现生物利用。其他组织如何获得和处理这些铁仍是未知数。本研究以心脏为背景探讨了这一问题:方法:对 12 名接受羧甲基亚铁(FCM)治疗缺铁的患者进行了前瞻性观察研究。纵向收集了心肌、脾脏和肝脏的磁共振弛豫时间和血浆铁标记物。为了检查心肌对铁吸收的处理情况,对 FCM 处理过的小鼠和细胞进行了细胞内易变铁池(LIP)成像:结果:在患者中,心肌松弛时间 T1 在 FCM 治疗后 3 小时达到最大值,42 天后仍保持较低水平,而脾脏 T1 在 14 天达到最大值,42 天后恢复。在血浆中,非转铁蛋白结合铁(NTBI)在 3 小时后达到峰值,而铁蛋白在 14 天后达到峰值。不同患者肝脏 T1 的变化各不相同。在小鼠中,心肌 LIP 在 FCM 1 小时后升高,42 天后仍保持升高。在心肌细胞中,暴露于 FCM 会迅速升高 LIP。NTBI转运体T型和L型钙通道以及二价金属转运体1的抑制剂可防止这种情况:结论:使用 FCM 进行静脉铁治疗可通过 NTBI 转运体将铁迅速输送到心肌,而不受网状内皮巨噬细胞的影响。这些铁在数周内仍不稳定,反映出心肌储存铁的能力有限。这些发现挑战了目前关于心脏如何从这些疗法中获得铁的观念,并凸显了长期用药导致铁在心脏中累积的可能性。
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来源期刊
European Heart Journal
European Heart Journal 医学-心血管系统
CiteScore
39.30
自引率
6.90%
发文量
3942
审稿时长
1 months
期刊介绍: The European Heart Journal is a renowned international journal that focuses on cardiovascular medicine. It is published weekly and is the official journal of the European Society of Cardiology. This peer-reviewed journal is committed to publishing high-quality clinical and scientific material pertaining to all aspects of cardiovascular medicine. It covers a diverse range of topics including research findings, technical evaluations, and reviews. Moreover, the journal serves as a platform for the exchange of information and discussions on various aspects of cardiovascular medicine, including educational matters. In addition to original papers on cardiovascular medicine and surgery, the European Heart Journal also presents reviews, clinical perspectives, ESC Guidelines, and editorial articles that highlight recent advancements in cardiology. Additionally, the journal actively encourages readers to share their thoughts and opinions through correspondence.
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