title: Endothelial-to-mesenchymal transition in pulmonary hypertension.
abstract: BACKGROUND
  The vascular remodeling responsible for pulmonary arterial hypertension (PAH) involves predominantly the accumulation of α-smooth muscle actin-expressing mesenchymal-like cells in obstructive pulmonary vascular lesions. Endothelial-to-mesenchymal transition (EndoMT) may be a source of those α-smooth muscle actin-expressing cells.
  
  
  RESULTS
  In situ evidence of EndoMT in human PAH was obtained by using confocal microscopy of multiple fluorescent stainings at the arterial level, and by using transmission electron microscopy and correlative light and electron microscopy at the ultrastructural level. Findings were confirmed by in vitro analyses of human PAH and control cultured pulmonary artery endothelial cells. In addition, the mRNA and protein signature of EndoMT was recognized at the arterial and lung level by quantitative real-time polymerase chain reaction and Western blot analyses. We confirmed our human observations in established animal models of pulmonary hypertension (monocrotaline and SuHx). After establishing the first genetically modified rat model linked to BMPR2 mutations (BMPR2(Δ140Ex1/+) rats), we demonstrated that EndoMT is linked to alterations in signaling of BMPR2, a gene that is mutated in 70% of cases of familial PAH and in 10% to 40% of cases of idiopathic PAH. We identified molecular actors of this pathological transition, including twist overexpression and vimentin phosphorylation. We demonstrated that rapamycin partially reversed the protein expression patterns of EndoMT, improved experimental PAH, and decreased the migration of human pulmonary artery endothelial cells, providing the proof of concept that EndoMT is druggable.
  
  
  CONCLUSIONS
  EndoMT is linked to alterations in BPMR2 signaling and is involved in the occlusive vas cular remodeling of PAH, findings that may have therapeutic implications.
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Benoît
authors.initials: B
authors.lastname: Ranchoux
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Fabrice
authors.initials: F
authors.lastname: Antigny
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Catherine
authors.initials: C
authors.lastname: Rucker-Martin
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Aurélie
authors.initials: A
authors.lastname: Hautefort
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Christine
authors.initials: C
authors.lastname: Péchoux
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Harm Jan
authors.initials: HJ
authors.lastname: Bogaard
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Séverine
authors.initials: S
authors.lastname: Remy
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Florence
authors.initials: F
authors.lastname: Lecerf
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Sylvie
authors.initials: S
authors.lastname: Planté
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Sophie
authors.initials: S
authors.lastname: Chat
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Elie
authors.initials: E
authors.lastname: Fadel
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Amal
authors.initials: A
authors.lastname: Houssaini
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Serge
authors.initials: S
authors.lastname: Adnot
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Gerald
authors.initials: G
authors.lastname: Simonneau
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).
authors.forename: Sylvia
authors.initials: S
authors.lastname: Cohen-Kaminsky
authors.affiliation: From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.). frederic.perros@inserm.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Perros
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D015415:Biomarkers; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000096:biosynthesis / Q000235:genetics; D002465:Cell Movement; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D000860:Hypoxia / Q000150:complications; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008648:Mesoderm / Q000473:pathology*; D016686:Monocrotaline / Q000633:toxicity; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology; D066253:Vascular Remodeling; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000199:Actins; D015415:Biomarkers; D012333:RNA, Messenger; D014746:Vimentin; D016686:Monocrotaline; D052006:Bone Morphogenetic Protein Receptors, Type II; D020123:Sirolimus
keywords: TWIST1 protein, human; bone morphogenetic protein receptors, type II; cardiovascular diseases; epithelial-mesenchymal transition; hypertension, pulmonary; models, animal; neointima; sirolimus; vascular remodeling; vimentin