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5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure

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-...

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Autores principales: Janssen, Wiebke, Schymura, Yves, Novoyatleva, Tatyana, Kojonazarov, Baktybek, Boehm, Mario, Wietelmann, Astrid, Luitel, Himal, Murmann, Kirsten, Krompiec, Damian Richard, Tretyn, Aleksandra, Pullamsetti, Soni Savai, Weissmann, Norbert, Seeger, Werner, Ghofrani, Hossein Ardeschir, Schermuly, Ralph Theo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312574/
https://www.ncbi.nlm.nih.gov/pubmed/25667920
http://dx.doi.org/10.1155/2015/438403
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author Janssen, Wiebke
Schymura, Yves
Novoyatleva, Tatyana
Kojonazarov, Baktybek
Boehm, Mario
Wietelmann, Astrid
Luitel, Himal
Murmann, Kirsten
Krompiec, Damian Richard
Tretyn, Aleksandra
Pullamsetti, Soni Savai
Weissmann, Norbert
Seeger, Werner
Ghofrani, Hossein Ardeschir
Schermuly, Ralph Theo
author_facet Janssen, Wiebke
Schymura, Yves
Novoyatleva, Tatyana
Kojonazarov, Baktybek
Boehm, Mario
Wietelmann, Astrid
Luitel, Himal
Murmann, Kirsten
Krompiec, Damian Richard
Tretyn, Aleksandra
Pullamsetti, Soni Savai
Weissmann, Norbert
Seeger, Werner
Ghofrani, Hossein Ardeschir
Schermuly, Ralph Theo
author_sort Janssen, Wiebke
collection PubMed
description 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. Conclusion. 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.
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spelling pubmed-43125742015-02-09 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure Janssen, Wiebke Schymura, Yves Novoyatleva, Tatyana Kojonazarov, Baktybek Boehm, Mario Wietelmann, Astrid Luitel, Himal Murmann, Kirsten Krompiec, Damian Richard Tretyn, Aleksandra Pullamsetti, Soni Savai Weissmann, Norbert Seeger, Werner Ghofrani, Hossein Ardeschir Schermuly, Ralph Theo Biomed Res Int Research Article 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. Conclusion. 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. Hindawi Publishing Corporation 2015 2015-02-01 /pmc/articles/PMC4312574/ /pubmed/25667920 http://dx.doi.org/10.1155/2015/438403 Text en Copyright © 2015 Wiebke Janssen et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Janssen, Wiebke
Schymura, Yves
Novoyatleva, Tatyana
Kojonazarov, Baktybek
Boehm, Mario
Wietelmann, Astrid
Luitel, Himal
Murmann, Kirsten
Krompiec, Damian Richard
Tretyn, Aleksandra
Pullamsetti, Soni Savai
Weissmann, Norbert
Seeger, Werner
Ghofrani, Hossein Ardeschir
Schermuly, Ralph Theo
5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure
title 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure
title_full 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure
title_fullStr 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure
title_full_unstemmed 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure
title_short 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure
title_sort 5-ht2b receptor antagonists inhibit fibrosis and protect from rv heart failure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312574/
https://www.ncbi.nlm.nih.gov/pubmed/25667920
http://dx.doi.org/10.1155/2015/438403
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