Bone Morphogenetic Protein Receptor Type 2 Mutation in Pulmonary Arterial Hypertension: A View on the Right Ventricle.

Autor:	van der Bruggen CE; 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.)., Happé CM; 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.)., Dorfmüller P; 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.)., Trip P; 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.)., Spruijt OA; 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.)., Rol N; 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.)., Hoevenaars FP; 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.)., Houweling AC; 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.)., Girerd B; 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.)., Marcus JT; 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.)., Mercier O; 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.)., Humbert M; 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.)., Handoko ML; 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.)., van der Velden J; 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.)., Vonk Noordegraaf A; 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.)., Bogaard HJ; 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.)., Goumans MJ; 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.)., de Man FS; 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.
Jazyk:	angličtina
Zdroj:	Circulation [Circulation] 2016 May 03; Vol. 133 (18), pp. 1747-60. Date of Electronic Publication: 2016 Mar 16.
DOI:	10.1161/CIRCULATIONAHA.115.020696
Abstrakt:	Background: 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. Methods and Results: 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. Conclusions: 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. (© 2016 American Heart Association, Inc.)
Databáze:	MEDLINE
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