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Reduction of BMPR2 mRNA Expression in Peripheral Blood of Pulmonary Arterial Hypertension Patients: A Marker for Disease Severity?

Pulmonary arterial hypertension (PAH) can be caused by pathogenic variants in the gene bone morphogenetic protein receptor 2 (BMPR2). While BMPR2 protein expression levels are known to be reduced in the lung tissue of heritable PAH (HPAH) patients, a systematic study evaluating expression in more ea...

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Autores principales: Theobald, Vivienne, Benjamin, Nicola, Seyfarth, Hans-Jürgen, Halank, Michael, Schneider, Marc A., Richtmann, Sarah, Hinderhofer, Katrin, Xanthouli, Panagiota, Egenlauf, Benjamin, Seeger, Rebekka, Hoeper, Marius M., Jonigk, Danny, Grünig, Ekkehard, Eichstaedt, Christina A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141548/
https://www.ncbi.nlm.nih.gov/pubmed/35627145
http://dx.doi.org/10.3390/genes13050759
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author Theobald, Vivienne
Benjamin, Nicola
Seyfarth, Hans-Jürgen
Halank, Michael
Schneider, Marc A.
Richtmann, Sarah
Hinderhofer, Katrin
Xanthouli, Panagiota
Egenlauf, Benjamin
Seeger, Rebekka
Hoeper, Marius M.
Jonigk, Danny
Grünig, Ekkehard
Eichstaedt, Christina A.
author_facet Theobald, Vivienne
Benjamin, Nicola
Seyfarth, Hans-Jürgen
Halank, Michael
Schneider, Marc A.
Richtmann, Sarah
Hinderhofer, Katrin
Xanthouli, Panagiota
Egenlauf, Benjamin
Seeger, Rebekka
Hoeper, Marius M.
Jonigk, Danny
Grünig, Ekkehard
Eichstaedt, Christina A.
author_sort Theobald, Vivienne
collection PubMed
description Pulmonary arterial hypertension (PAH) can be caused by pathogenic variants in the gene bone morphogenetic protein receptor 2 (BMPR2). While BMPR2 protein expression levels are known to be reduced in the lung tissue of heritable PAH (HPAH) patients, a systematic study evaluating expression in more easily accessible blood samples and its clinical relevance is lacking. Thus, we analyzed the BMPR2 mRNA expression in idiopathic/HPAH patients and healthy controls in blood by quantitative polymerase chain reaction and protein expression by enzyme-linked immunosorbent assay. Clinical parameters included right heart catherization, echocardiography, six-minute walking test and laboratory tests. BMPR2 variant-carriers (n = 23) showed significantly lower BMPR2 mRNA expression in comparison to non-carriers (n = 56) and healthy controls (n = 30; p < 0.0001). No difference in BMPR2 protein expression was detected. Lower BMPR2 mRNA expression correlated significantly with greater systolic pulmonary artery pressure and pulmonary vascular resistance. Higher BMPR2 mRNA expression correlated with greater glomerular filtration rate, cardiac index and six-minute walking distance. We demonstrated the feasibility to assess BMPR2 expression in blood and, for the first time, that BMPR2 mRNA expression levels are significantly reduced in variant carriers and correlated with clinical parameters. Further studies may evaluate the usefulness of BMPR2 mRNA expression in blood as a new marker for disease severity.
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spelling pubmed-91415482022-05-28 Reduction of BMPR2 mRNA Expression in Peripheral Blood of Pulmonary Arterial Hypertension Patients: A Marker for Disease Severity? Theobald, Vivienne Benjamin, Nicola Seyfarth, Hans-Jürgen Halank, Michael Schneider, Marc A. Richtmann, Sarah Hinderhofer, Katrin Xanthouli, Panagiota Egenlauf, Benjamin Seeger, Rebekka Hoeper, Marius M. Jonigk, Danny Grünig, Ekkehard Eichstaedt, Christina A. Genes (Basel) Article Pulmonary arterial hypertension (PAH) can be caused by pathogenic variants in the gene bone morphogenetic protein receptor 2 (BMPR2). While BMPR2 protein expression levels are known to be reduced in the lung tissue of heritable PAH (HPAH) patients, a systematic study evaluating expression in more easily accessible blood samples and its clinical relevance is lacking. Thus, we analyzed the BMPR2 mRNA expression in idiopathic/HPAH patients and healthy controls in blood by quantitative polymerase chain reaction and protein expression by enzyme-linked immunosorbent assay. Clinical parameters included right heart catherization, echocardiography, six-minute walking test and laboratory tests. BMPR2 variant-carriers (n = 23) showed significantly lower BMPR2 mRNA expression in comparison to non-carriers (n = 56) and healthy controls (n = 30; p < 0.0001). No difference in BMPR2 protein expression was detected. Lower BMPR2 mRNA expression correlated significantly with greater systolic pulmonary artery pressure and pulmonary vascular resistance. Higher BMPR2 mRNA expression correlated with greater glomerular filtration rate, cardiac index and six-minute walking distance. We demonstrated the feasibility to assess BMPR2 expression in blood and, for the first time, that BMPR2 mRNA expression levels are significantly reduced in variant carriers and correlated with clinical parameters. Further studies may evaluate the usefulness of BMPR2 mRNA expression in blood as a new marker for disease severity. MDPI 2022-04-26 /pmc/articles/PMC9141548/ /pubmed/35627145 http://dx.doi.org/10.3390/genes13050759 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Theobald, Vivienne
Benjamin, Nicola
Seyfarth, Hans-Jürgen
Halank, Michael
Schneider, Marc A.
Richtmann, Sarah
Hinderhofer, Katrin
Xanthouli, Panagiota
Egenlauf, Benjamin
Seeger, Rebekka
Hoeper, Marius M.
Jonigk, Danny
Grünig, Ekkehard
Eichstaedt, Christina A.
Reduction of BMPR2 mRNA Expression in Peripheral Blood of Pulmonary Arterial Hypertension Patients: A Marker for Disease Severity?
title Reduction of BMPR2 mRNA Expression in Peripheral Blood of Pulmonary Arterial Hypertension Patients: A Marker for Disease Severity?
title_full Reduction of BMPR2 mRNA Expression in Peripheral Blood of Pulmonary Arterial Hypertension Patients: A Marker for Disease Severity?
title_fullStr Reduction of BMPR2 mRNA Expression in Peripheral Blood of Pulmonary Arterial Hypertension Patients: A Marker for Disease Severity?
title_full_unstemmed Reduction of BMPR2 mRNA Expression in Peripheral Blood of Pulmonary Arterial Hypertension Patients: A Marker for Disease Severity?
title_short Reduction of BMPR2 mRNA Expression in Peripheral Blood of Pulmonary Arterial Hypertension Patients: A Marker for Disease Severity?
title_sort reduction of bmpr2 mrna expression in peripheral blood of pulmonary arterial hypertension patients: a marker for disease severity?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141548/
https://www.ncbi.nlm.nih.gov/pubmed/35627145
http://dx.doi.org/10.3390/genes13050759
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