Department of Physiology, Anatomy & Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, United Kingdom.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
Eur Heart J. 2024 Nov 8;45(42):4497-4508. doi: 10.1093/eurheartj/ehae359.
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.
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.
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.
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.
静脉铁治疗含有铁-碳水化合物复合物，旨在通过脾和肝网状内皮巨噬细胞确保铁变得可用。其他组织如何获得和处理这种铁仍然未知。本研究在心脏背景下探讨了这个问题。
对 12 例接受羧基麦芽糖铁（FCM）治疗缺铁的患者进行前瞻性观察研究。纵向收集心肌、脾和肝磁共振弛豫时间和血浆铁标志物。为了研究心肌摄取铁的处理方式，在 FCM 处理的小鼠和细胞中对细胞内不稳定铁池（LIP）进行成像。
在患者中，心肌弛豫时间 T1 在 FCM 后 3 小时最大程度下降，42 天后仍保持低值，而脾脏 T1 在 14 天最大程度下降，42 天后恢复。在血浆中，非转铁蛋白结合铁（NTBI）在 3 小时达到峰值，而铁蛋白在 14 天达到峰值。肝 T1 的变化在患者中存在差异。在小鼠中，心肌 LIP 在 FCM 后 1 小时升高，并持续升高 42 天。在心肌细胞中，FCM 暴露会迅速增加 LIP。这可以通过抑制 NTBI 转运体 T 型和 L 型钙通道和二价金属转运蛋白 1 来预防。
FCM 静脉铁治疗通过 NTBI 转运体迅速将铁输送到心肌，与网状内皮巨噬细胞无关。这种铁在数周内仍然不稳定，反映了心肌有限的铁储存能力。这些发现挑战了目前关于心脏如何从这些治疗中获取铁的观点，并强调了长期给药可能导致心脏中铁的累积。
