Clin Res Cardiol (2021)
DOI DOI https://doi.org/10.1007/s00392-021-01843-w
Association between BMPR2 mutations and iron metabolism in pulmonary arterial hypertension patients
V. Theobald1, E. Grünig1, N. Benjamin1, B. Egenlauf2, H. Gall3, G. Ardeschir3, M. Halank4, S. Harutyunova1, M. Hoeper5, D. Jonigk5, M. Schneider1, H.-J. Seyfarth6, S. Richtmann1, P. Xanthouli1, M. Muckenthaler7, C. Eichstaedt8
1Thoraxklinik, Universitätsklinikum Heidelberg, Heidelberg; 2Pneumologie und Beatmungsmedizin / Zentrum für Pulmonale Hypertonie, Thoraxklinik - Heidelberg gGmbH, Heidelberg; 3Universitätsklinikum Gießen und Marburg GmbH, Gießen; 4Medizinische Klinik I, Universitätsklinikum Carl Gustav Carus an der TU Dresden, Dresden; 5Abteilung Pneumologie, Medizinische Hochschule Hannover, Hannover; 6Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig; 7Universitätsklinikum Heidelberg, Heidelberg; 8Thoraxklinik - Heidelberg gGmbH, Heidelberg;

Background: Iron deficiency is common in pulmonary arterial hypertension (PAH) patients and might be caused by a dysregulation of the hormone hepcidin, which is upregulated by the binding to the bone morphogenetic protein receptor 2 (BMPR2).

Objective: The aim of this study was to assess whether hepcidin and BMPR2 expression are correlated and influence clinical parameters in PAH-patients with or without BMPR2 mutation and healthy controls.

Methods: In this explorative cross-sectional study BMPR2 expression in peripheral blood cells was measured in 21 heritable PAH (HPAH; BMPR2 mutation carriers), 60 idiopathic PAH (IPAH) patients and 30 healthy controls by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). The primary endpoint was the relationship between hepcidin and BMPR2 expression in mutation carriers and non-carriers. Statistical analysis was performed with the Kruskal-Wallis test for independent samples.  

Results: 81 PAH patients and 30 healthy controls have been successfully enrolled. Samples of BMPR2 mutation carriers in comparison to non-carriers and healthy controls showed significantly lower BMPR2 mRNA expression levels (p<0.0001, Figure 1). There was no significant difference concerning hepcidin values between the groups.

Discussion: The BMPR2 mutations most likely explain the reduced messenger RNA expression levels in mutation carriers.  While we expected this reduction to lead to higher hepcidin values, this was not the case in our study. Increased hepcidin signals iron abundance and can lead to a more severe iron deficiency. However, hepcidin is regulated by numerous pathways and so the effect of BMPR2 expression concerning hepcidin values might have become overshadowed.

Conclusion: BMPR2 mutation carriers showed lower BMPR2 mRNA expression levels in peripheral blood compared to non-carriers and healthy controls. A significant difference in hepcidin values could not be detected.


Figure 1: Mean relative BMPR2 expression in whole blood

Mean relative BMPR2 mRNA expression in whole blood from BMPR2 mutation carriers, non-carriers and healthy controls.



https://dgk.org/kongress_programme/jt2021/aP1470.html