{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:11:57Z","timestamp":1790629917826,"version":"4.1.0"},"reference-count":17,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"publisher","award":["82DZLB44A2"],"award-info":[{"award-number":["82DZLB44A2"]}],"id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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 &lt; 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.<\/jats:p>","DOI":"10.3390\/genes13050759","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T11:45:55Z","timestamp":1650973555000},"page":"759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Reduction of BMPR2 mRNA Expression in Peripheral Blood of Pulmonary Arterial Hypertension Patients: A Marker for Disease Severity?"],"prefix":"10.3390","volume":"13","author":[{"given":"Vivienne","family":"Theobald","sequence":"first","affiliation":[{"name":"Center for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital, 69126 Heidelberg, Germany"},{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Center for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital, 69126 Heidelberg, Germany"},{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-J\u00fcrgen","family":"Seyfarth","sequence":"additional","affiliation":[{"name":"Department of Pneumology, Medical Clinic II, University Hospital of Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Halank","sequence":"additional","affiliation":[{"name":"Medical Clinic I, University Hospital of Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8269-3821","authenticated-orcid":false,"given":"Marc A.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany"},{"name":"Translational Research Unit, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital, 69126 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-8297","authenticated-orcid":false,"given":"Sarah","family":"Richtmann","sequence":"additional","affiliation":[{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany"},{"name":"Translational Research Unit, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital, 69126 Heidelberg, Germany"},{"name":"Division of Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Hinderhofer","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Diagnostics, Institute of Human Genetics, Heidelberg University, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota","family":"Xanthouli","sequence":"additional","affiliation":[{"name":"Center for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital, 69126 Heidelberg, Germany"},{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2466-1420","authenticated-orcid":false,"given":"Benjamin","family":"Egenlauf","sequence":"additional","affiliation":[{"name":"Center for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital, 69126 Heidelberg, Germany"},{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekka","family":"Seeger","sequence":"additional","affiliation":[{"name":"Center for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital, 69126 Heidelberg, Germany"},{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9086-2293","authenticated-orcid":false,"given":"Marius M.","family":"Hoeper","sequence":"additional","affiliation":[{"name":"Clinic for Pneumology, Hannover Medical School, Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-2281","authenticated-orcid":false,"given":"Danny","family":"Jonigk","sequence":"additional","affiliation":[{"name":"Institute for Pathology, Hannover Medical School, Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Gr\u00fcnig","sequence":"additional","affiliation":[{"name":"Center for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital, 69126 Heidelberg, Germany"},{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7288-8297","authenticated-orcid":false,"given":"Christina A.","family":"Eichstaedt","sequence":"additional","affiliation":[{"name":"Center for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital, 69126 Heidelberg, Germany"},{"name":"Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany"},{"name":"Laboratory for Molecular Diagnostics, Institute of Human Genetics, Heidelberg University, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1183\/13993003.01032-2015","article-title":"2015 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)","volume":"46","author":"Humbert","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1042\/CS20160531","article-title":"Identification of genetic defects in pulmonary arterial hypertension by a new gene panel diagnostic tool","volume":"130","author":"Song","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1016\/j.jacc.2009.04.015","article-title":"Genetics and genomics of pulmonary arterial hypertension","volume":"54","author":"Machado","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/1465-9921-12-99","article-title":"Hemodynamic and clinical onset in patients with hereditary pulmonary arterial hypertension and BMPR2 mutations","volume":"12","author":"Pfarr","year":"2011","journal-title":"Respir. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12931-016-0457-x","article-title":"EIF2AK4 mutation as \u201csecond hit\u201d in hereditary pulmonary arterial hypertension","volume":"17","author":"Eichstaedt","year":"2016","journal-title":"Respir. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1161\/01.CIR.0000012754.72951.3D","article-title":"Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor","volume":"105","author":"Atkinson","year":"2002","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ajpath.2011.03.040","article-title":"Plexiform lesions in pulmonary arterial hypertension composition, architecture, and microenvironment","volume":"179","author":"Jonigk","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S2213-2600(15)00544-5","article-title":"BMPR2 mutations and survival in pulmonary arterial hypertension: An individual participant data meta-analysis","volume":"4","author":"Evans","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hinderhofer, K., Fischer, C., Pfarr, N., Szamalek-Hoegel, J., Lichtblau, M., Nagel, C., Egenlauf, B., Ehlken, N., and Gr\u00fcnig, E. (2014). Identification of a new intronic BMPR2-mutation and early diagnosis of heritable pulmonary arterial hypertension in a large family with mean clinical follow-up of 12 years. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091374"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2004229","DOI":"10.1183\/13993003.04229-2020","article-title":"Screening for pulmonary arterial hypertension in adults carrying a BMPR2 mutation","volume":"58","author":"Montani","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Eichstaedt, C.A., Verweyen, J., Halank, M., Benjamin, N., Fischer, C., Mayer, E., Guth, S., Wiedenroth, C.B., Egenlauf, B., and Harutyunova, S. (2020). Myeloproliferative Diseases as Possible Risk Factor for Development of Chronic Thromboembolic Pulmonary Hypertension-A Genetic Study. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093339"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1158\/1078-0432.CCR-14-2464","article-title":"Glycodelin: A New Biomarker with Immunomodulatory Functions in Non-Small Cell Lung Cancer","volume":"21","author":"Schneider","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1602449","DOI":"10.1183\/13993003.02449-2016","article-title":"Randomised placebo-controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension","volume":"50","author":"Spiekerkoetter","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1056\/NEJMoa2024277","article-title":"Sotatercept for the Treatment of Pulmonary Arterial Hypertension","volume":"384","author":"Humbert","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12931-022-01987-x","article-title":"Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension","volume":"23","author":"Eichstaedt","year":"2022","journal-title":"Respir. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"170093","DOI":"10.1183\/16000617.0093-2017","article-title":"Pathobiology of pulmonary arterial hypertension: Understanding the roads less travelled","volume":"26","author":"Hemnes","year":"2017","journal-title":"Eur. Respir. Rev."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/759\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:01:08Z","timestamp":1760137268000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,26]]},"references-count":17,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["genes13050759"],"URL":"https:\/\/doi.org\/10.3390\/genes13050759","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,26]]}}}