Bone morphogenetic protein 10 is increased in pre-capillary pulmonary hypertension patients
Cardiovascular Research, vol. 121, pp. 1254–1268
Abstract
AIMS: Pre-capillary pulmonary hypertension (precPH) results in increased right atrial (RA) stretch and pressure. The right atrium is the major source of bone morphogenetic protein 10 (BMP10) in adults, primarily produced by RA cardiomyocytes. The aim of this study was to investigate BMP10 expression in the right heart and systemic circulation and to identify potential triggers for increased BMP10 secretion associated with precPH. METHODS AND RESULTS: We examined BMP10 mRNA and protein expressions in RA tissue. Circulating BMP10 plasma levels were determined using enzyme-linked immunosorbent assay. BMP10 transcriptional activity was studied using a BMP-responsive element luciferase assay. Correlation analyses were performed between circulating BMP10 and RA dilatation as well as right ventricular (RV) function. Finally, we determined the impact of pressure unloading on BMP10 activity in chronic thromboembolic pulmonary hypertension (CTEPH) patients before and after pulmonary endarterectomy (PEA). BMP10 mRNA's protein and activity were significantly increased in the precPH right atrium. While circulating BMP10 protein levels were elevated, no significant changes were observed in BMP10 transcriptional activity between precPH and controls. Interestingly, RA dilatation, increased RA pressure, high N-terminal pro b-type natriuretic peptide levels, and reduced RV ejection fraction were associated with high BMP10 activity. Finally, pressure unloading after PEA in a cohort of CTEPH patients resulted in reduced BMP10 activity. CONCLUSION: RA BMP10 expression and plasma levels are increased in precPH, likely triggered by excessive RA dilatation and pressure overload. Future studies are needed to determine whether increased BMP10 release is an adaptive mechanism or a potential therapeutic target.
Authors 18
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Amsterdam Cardiovascular Sciences · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis , De Boelelaan 1117, 1081HV Amsterdam ,
Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX laboratory, Department of Pulmonary Medicine, Amsterdam, The Netherlands
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Amsterdam Cardiovascular Sciences · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis , De Boelelaan 1117, 1081HV Amsterdam ,
Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX laboratory, Department of Pulmonary Medicine, Amsterdam, The Netherlands
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Amsterdam Cardiovascular Sciences · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis , De Boelelaan 1117, 1081HV Amsterdam ,
Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX laboratory, Department of Pulmonary Medicine, Amsterdam, The Netherlands
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Amsterdam Cardiovascular Sciences · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis , De Boelelaan 1117, 1081HV Amsterdam ,
Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX laboratory, Department of Pulmonary Medicine, Amsterdam, The Netherlands
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Gonzalo Sánchez‐Duffhues Aachen Department of Cell and Chemical Biology Department of Cell and Chemical Biology
Leiden University · Consejo Superior de Investigaciones Científicas · Leiden University Medical Center · Nanomaterials and Nanotechnology Research Center · Instituto de Investigación Sanitaria del Principado de Asturias
Affiliation as printed
Department of Cell and Chemical Biology, Leiden UMC , Einthovenweg 20, 2333 ZC Leiden ,
Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA) , Av. del Hospital Universitario s/n, 33011 Oviedo, Asturias ,
Department of Cell and Chemical Biology, Leiden UMC, Leiden, The Netherlands
Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Oviedo, Asturias, Spain
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Clarissa Becher Aachen Department of Cell and Chemical Biology Department of Cell and Chemical Biology
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology, Leiden UMC , Einthovenweg 20, 2333 ZC Leiden ,
Department of Cell and Chemical Biology, Leiden UMC, Leiden, The Netherlands
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Amsterdam Cardiovascular Sciences · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis , De Boelelaan 1117, 1081HV Amsterdam ,
Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX laboratory, Department of Pulmonary Medicine, Amsterdam, The Netherlands
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Amsterdam Cardiovascular Sciences · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis , De Boelelaan 1117, 1081HV Amsterdam ,
Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX laboratory, Department of Pulmonary Medicine, Amsterdam, The Netherlands
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Amsterdam Cardiovascular Sciences · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis , De Boelelaan 1117, 1081HV Amsterdam ,
Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX laboratory, Department of Pulmonary Medicine, Amsterdam, The Netherlands
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Cardiology, Amsterdam UMC location Vrije Universiteit Amsterdam , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Cardiology, Amsterdam, The Netherlands
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Radiology and Nuclear Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam, The Netherlands
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Radiology and Nuclear Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam, The Netherlands
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Cardiothoracic Surgery, Amsterdam UMC location Vrije Universiteit Amsterdam , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Cardiothoracic Surgery, Amsterdam, The Netherlands
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Pathology, Amsterdam UMC location Vrije Universiteit Amsterdam , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Pathology, Amsterdam, The Netherlands
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Amsterdam Cardiovascular Sciences · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis , De Boelelaan 1117, 1081HV Amsterdam ,
Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX laboratory, Department of Pulmonary Medicine, Amsterdam, The Netherlands
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Amsterdam Cardiovascular Sciences · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis , De Boelelaan 1117, 1081HV Amsterdam ,
Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX laboratory, Department of Pulmonary Medicine, Amsterdam, The Netherlands
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Marie‐José Goumans corresponding Aachen Department of Cell and Chemical Biology Department of Cell and Chemical Biology
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology, Leiden UMC , Einthovenweg 20, 2333 ZC Leiden ,
Department of Cell and Chemical Biology, Leiden UMC, Leiden, The Netherlands
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Frances S. de Man corresponding
Amsterdam Cardiovascular Sciences · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis , De Boelelaan 1117, 1081HV Amsterdam ,
Department of Pulmonary Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX Laboratory , De Boelelaan 1117, 1081HV Amsterdam ,
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands
Amsterdam UMC location Vrije Universiteit Amsterdam, PHEniX laboratory, Department of Pulmonary Medicine, Amsterdam, The Netherlands
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