title: 5-HT2B receptor antagonists inhibit fibrosis and protect from RV heart failure.
abstract: OBJECTIVE
  The serotonin (5-HT) pathway was shown to play a role in pulmonary hypertension (PH), but its functions in right ventricular failure (RVF) remain poorly understood. The aim of the current study was to investigate the effects of Terguride (5-HT2A and 2B receptor antagonist) or SB204741 (5-HT2B receptor antagonist) on right heart function and structure upon pulmonary artery banding (PAB) in mice.
  
  
  METHODS
  Seven days after PAB, mice were treated for 14 days with Terguride (0.2 mg/kg bid) or SB204741 (5 mg/kg day). Right heart function and remodeling were assessed by right heart catheterization, magnetic resonance imaging (MRI), and histomorphometric methods. Total secreted collagen content was determined in mouse cardiac fibroblasts isolated from RV tissues.
  
  
  RESULTS
  Chronic treatment with Terguride or SB204741 reduced right ventricular fibrosis and showed improved heart function in mice after PAB. Moreover, 5-HT2B receptor antagonists diminished TGF-beta1 induced collagen synthesis of RV cardiac fibroblasts in vitro.
  
  
  CONCLUSIONS
  5-HT2B receptor antagonists reduce collagen deposition, thereby inhibiting right ventricular fibrosis. Chronic treatment prevented the development and progression of pressure overload-induced RVF in mice. Thus, 5-HT2B receptor antagonists represent a valuable novel therapeutic approach for RVF.
authors: Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany ; German Center for Lung Research (DZL), 35392 Giessen, Germany.
authors: Wiebke
authors: W
authors: Janssen
authors: Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors: Yves
authors: Y
authors: Schymura
authors: Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany ; German Center for Lung Research (DZL), 35392 Giessen, Germany.
authors: Tatyana
authors: T
authors: Novoyatleva
authors: Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany ; German Center for Lung Research (DZL), 35392 Giessen, Germany.
authors: Baktybek
authors: 0000-0002-3252-359X
authors: B
authors: Kojonazarov
authors: Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany ; German Center for Lung Research (DZL), 35392 Giessen, Germany.
authors: Mario
authors: 0000-0003-4070-438X
authors: M
authors: Boehm
authors: Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors: Astrid
authors: 0000-0003-1626-1961
authors: A
authors: Wietelmann
authors: Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany ; German Center for Lung Research (DZL), 35392 Giessen, Germany.
authors: Himal
authors: H
authors: Luitel
authors: Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany ; German Center for Lung Research (DZL), 35392 Giessen, Germany.
authors: Kirsten
authors: 0000-0003-1617-063X
authors: K
authors: Murmann
authors: Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany ; German Center for Lung Research (DZL), 35392 Giessen, Germany.
authors: Damian Richard
authors: 0000-0001-8387-574X
authors: DR
authors: Krompiec
authors: Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors: Aleksandra
authors: A
authors: Tretyn
authors: Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors: Soni Savai
authors: SS
authors: Pullamsetti
authors: Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany ; German Center for Lung Research (DZL), 35392 Giessen, Germany.
authors: Norbert
authors: N
authors: Weissmann
authors: Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany ; German Center for Lung Research (DZL), 35392 Giessen, Germany ; Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors: Werner
authors: W
authors: Seeger
authors: Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany ; German Center for Lung Research (DZL), 35392 Giessen, Germany.
authors: Hossein Ardeschir
authors: HA
authors: Ghofrani
authors: Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany ; German Center for Lung Research (DZL), 35392 Giessen, Germany.
authors: Ralph Theo
authors: RT
authors: Schermuly
mesh_terms: D000818:Animals; D004719:Endomyocardial Fibrosis / Q000378:metabolism / Q000517:prevention & control; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D044403:Receptor, Serotonin, 5-HT2B / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D018497:Ventricular Dysfunction, Right / Q000378:metabolism*
chemical_list: D020011:Protective Agents; D044403:Receptor, Serotonin, 5-HT2B; D058830:Serotonin 5-HT2 Receptor Antagonists