title: Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension: A View on the Right Ventricle.
abstract: The effect of a mutation in the bone morphogenetic protein receptor 2 (BMPR2) gene on right ventricular (RV) pressure overload in patients with pulmonary arterial hypertension is unknown. Therefore, we investigated RV function in patients who have pulmonary arterial hypertension with and without the BMPR2 mutation by combining in vivo measurements with molecular and histological analysis of human RV and left ventricular tissue.
  
  
  
  In total, 95 patients with idiopathic or familial pulmonary arterial hypertension were genetically screened for the presence of a BMPR2 mutation: 28 patients had a BMPR2 mutation, and 67 patients did not have a BMPR2 mutation. In vivo measurements were assessed using right heart catheterization and cardiac MRI. Despite a similar mean pulmonary artery pressure (noncarriers 54±15 versus mutation carriers 55±9 mm Hg) and pulmonary vascular resistance (755 [483-1043] versus 931 [624-1311] dynes·s(-1)·cm(-5)), mutation carriers presented with a more severely compromised RV function (RV ejection fraction: 37.6±12.8% versus 29.0±9%: P<0.05; cardiac index 2.7±0.9 versus 2.2±0.4 L·min(-1)·m(-2)). Differences continued to exist after treatment. To investigate the role of transforming growth factor β and bone morphogenetic protein receptor II signaling, human RV and left ventricular tissue were studied in controls (n=6), mutation carriers (n=5), and noncarriers (n=11). However, transforming growth factor β and bone morphogenetic protein receptor II signaling, and hypertrophy, apoptosis, fibrosis, capillary density, inflammation, and cardiac metabolism, as well, were similar between mutation carriers and noncarriers.
  
  
  
  Despite a similar afterload, RV function is more severely affected in mutation carriers than in noncarriers. However, these differences cannot be explained by a differential transforming growth factor β, bone morphogenetic protein receptor II signaling, or cardiac adaptation.
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Cathelijne E
authors.initials: CE
authors.lastname: van der Bruggen
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Chris M
authors.initials: CM
authors.lastname: Happé
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Pia
authors.initials: P
authors.lastname: Trip
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Onno A
authors.initials: OA
authors.lastname: Spruijt
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Nina
authors.initials: N
authors.lastname: Rol
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Femke P
authors.initials: FP
authors.lastname: Hoevenaars
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Houweling
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Barbara
authors.initials: B
authors.lastname: Girerd
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Marcus
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Olaf
authors.initials: O
authors.lastname: Mercier
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: M Louis
authors.initials: ML
authors.lastname: Handoko
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Jolanda
authors.initials: J
authors.lastname: van der Velden
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk Noordegraaf
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Harm Jan
authors.initials: HJ
authors.lastname: Bogaard
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.).
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Goumans
authors.affiliation: From Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.E.E.V.D.B., C.M.H., P.T., O.A.S., N.R., A.V.N., H.J.B., F.S.d.M.); Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (C.M.H., N.R., F.P.H., J.V.D.V., F.S.d.M.); Univ. Paris-Sud, Le Kremlin-Bicêtre, France (P.D., B.G., .M.H.); AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (P.D., B.G., M.H.); INSERM999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., B.G., M.H.); Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands (A.C.H.); Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands (J.T.M.); Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Hôpital Marie-Lannelongue, Le Plessis Robinson, Paris-Sud University, France (O.M.); Department of Cardiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (M.L.H.); and Department of Molecular Cell Biology, Laboratory of Experimental Cardiology, Leiden University Medical Center, Leiden, The Netherlands (M.-J.G.). fs.deman@vumc.nl.
authors.forename: Frances S
authors.initials: FS
authors.lastname: de Man
mesh_terms: D000328:Adult; D000368:Aged; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012189:Retrospective Studies; D018497:Ventricular Dysfunction, Right / Q000175:diagnosis / Q000235:genetics*; D016278:Ventricular Function, Right / Q000235:genetics*
chemical_list: C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II
keywords: genetics; heart failure; hypertension, pulmonary