title: Role of Nerve Growth Factor in Development and Persistence of Experimental Pulmonary Hypertension.
abstract: BACKGROUND
  Pulmonary hypertension (PH) is characterized by a progressive elevation in mean pulmonary arterial pressure, often leading to right ventricular failure and death. Growth factors play significant roles in the pathogenesis of PH, and their targeting may therefore offer novel therapeutic strategies in this disease.
  
  
  OBJECTIVE
  To evaluate the nerve growth factor (NGF) as a potential new target in PH.
  
  
  METHODS
  Expression and/or activation of NGF and its receptors were evaluated in rat experimental PH induced by chronic hypoxia or monocrotaline and in human PH (idiopathic or associated with chronic obstructive pulmonary disease). Effects of exogenous NGF were evaluated ex vivo on pulmonary arterial inflammation and contraction, and in vitro on pulmonary vascular cell proliferation, migration, and cytokine secretion. Effects of NGF inhibition were evaluated in vivo with anti-NGF blocking antibodies administered both in rat chronic hypoxia- and monocrotaline-induced PH.
  
  
  RESULTS
  Our results show increased expression of NGF and/or increased expression/activation of its receptors in experimental and human PH. Ex vivo/in vitro, we found out that NGF promotes pulmonary vascular cell proliferation and migration, pulmonary arterial hyperreactivity, and secretion of proinflammatory cytokines. In vivo, we demonstrated that anti-NGF blocking antibodies prevent and reverse PH in rats through significant reduction of pulmonary arterial inflammation, hyperreactivity, and remodeling.
  
  
  CONCLUSIONS
  This study highlights the critical role of NGF in PH. Because of the recent development of anti-NGF blocking antibodies as a possible new pain treatment, such a therapeutic strategy of NGF inhibition may be of interest in PH.
authors.affiliation: 1 University Bordeaux and.|2 INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, Bordeaux, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Freund-Michel
authors.affiliation: 1 University Bordeaux and.|2 INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, Bordeaux, France.
authors.forename: Marcelina
authors.initials: M
authors.lastname: Cardoso Dos Santos
authors.affiliation: 3 Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France.|4 INSERM UMR-S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Guignabert
authors.affiliation: 3 Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France.|4 INSERM UMR-S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.|5 Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, DHU Thorax Innovation, Assistance Publique Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France; and.
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.affiliation: 3 Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France.|4 INSERM UMR-S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Phan
authors.affiliation: 1 University Bordeaux and.|2 INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, Bordeaux, France.|6 CHU de Bordeaux, Bordeaux, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Coste
authors.affiliation: 3 Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France.|4 INSERM UMR-S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Ly
authors.initials: L
authors.lastname: Tu
authors.affiliation: 1 University Bordeaux and.|2 INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, Bordeaux, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Dubois
authors.affiliation: 3 Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France.|4 INSERM UMR-S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.|5 Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, DHU Thorax Innovation, Assistance Publique Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France; and.
authors.forename: Barbara
authors.initials: B
authors.lastname: Girerd
authors.affiliation: 1 University Bordeaux and.|2 INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, Bordeaux, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Courtois
authors.affiliation: 3 Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France.|4 INSERM UMR-S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.|5 Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, DHU Thorax Innovation, Assistance Publique Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France; and.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: 1 University Bordeaux and.|2 INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, Bordeaux, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.affiliation: 1 University Bordeaux and.|2 INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, Bordeaux, France.|6 CHU de Bordeaux, Bordeaux, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.affiliation: 1 University Bordeaux and.|2 INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, Bordeaux, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Muller
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020932:Nerve Growth Factor
keywords: animal disease models; blocking antibodies; pulmonary circulation