Theobald Vivienne, Grünig Ekkehard, Benjamin Nicola, Seyfarth Hans-Jürgen, Halank Michael, Schneider Marc A, Richtmann Sarah, Kazdal Daniel, Hinderhofer Katrin, Xanthouli Panagiota, Egenlauf Benjamin, Harutyunova Satenik, Hoeper Marius M, Jonigk Danny, Sparla Richard, Muckenthaler Martina U, Eichstaedt Christina A
Center for Pulmonary Hypertension Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital Heidelberg Germany.
Translational Lung Research Center Heidelberg (TLRC) German Center for Lung Research (DZL) Heidelberg Germany.
Pulm Circ. 2023 Jun 7;13(2):e12242. doi: 10.1002/pul2.12242. eCollection 2023 Apr.
Iron deficiency is common in idiopathic and heritable pulmonary arterial hypertension patients (I/HPAH). A previous report suggested a dysregulation of the iron hormone hepcidin, which is controlled by BMP/SMAD signaling involving the bone morphogenetic protein receptor 2 (BMPR-II). Pathogenic variants in the gene are the most common cause of HPAH. Their effect on patients' hepcidin levels has not been investigated. The aim of this study was to assess whether iron metabolism and regulation of the iron regulatory hormone hepcidin was disturbed in I/HPAH patients with and without a pathogenic variant in the gene compared to healthy controls. In this explorative, cross-sectional study hepcidin serum levels were quantified by enzyme-linked immunosorbent assay. We measured iron status, inflammatory parameters and hepcidin modifying proteins such as IL6, erythropoietin, and BMP2, BMP6 in addition to BMPR-II protein and mRNA levels. Clinical routine parameters were correlated with hepcidin levels. In total 109 I/HPAH patients and controls, separated into three groups, 23 variant-carriers, 56 noncarriers and 30 healthy controls were enrolled. Of these, 84% had iron deficiency requiring iron supplementation. Hepcidin levels were not different between groups and corresponded to the degree of iron deficiency. The levels of IL6, erythropoietin, BMP2, or BMP6 showed no correlation with hepcidin expression. Hence, iron homeostasis and hepcidin regulation was largely independent from these parameters. I/HPAH patients had a physiologically normal iron regulation and no false elevation of hepcidin levels. Iron deficiency was prevalent albeit independent of pathogenic variants in the gene.
缺铁在特发性和遗传性肺动脉高压患者（I/HPAH）中很常见。先前的一份报告表明，铁调节激素铁调素存在失调，其受涉及骨形态发生蛋白受体2（BMPR-II）的BMP/SMAD信号传导控制。该基因的致病性变异是HPAH最常见的原因。它们对患者铁调素水平的影响尚未得到研究。本研究的目的是评估与健康对照相比，有无该基因致病性变异的I/HPAH患者的铁代谢和铁调节激素铁调素的调节是否受到干扰。在这项探索性横断面研究中，通过酶联免疫吸附测定法定量铁调素血清水平。除了BMPR-II蛋白和mRNA水平外，我们还测量了铁状态、炎症参数以及铁调素调节蛋白，如IL6、促红细胞生成素和BMP2、BMP6。临床常规参数与铁调素水平相关。总共纳入了109名I/HPAH患者和对照，分为三组，23名变异携带者、56名非携带者和30名健康对照。其中，84%的人缺铁需要补充铁剂。各组之间铁调素水平没有差异，且与缺铁程度相对应。IL6、促红细胞生成素、BMP2或BMP6的水平与铁调素表达无相关性。因此，铁稳态和铁调素调节在很大程度上独立于这些参数。I/HPAH患者的铁调节在生理上正常，铁调素水平没有错误升高。缺铁很普遍，尽管与该基因的致病性变异无关。
