Research Article 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure Wiebke Janssen, 1,2 Yves Schymura, 3 Tatyana Novoyatleva, 1,2 Baktybek Kojonazarov, 1,2 Mario Boehm, 1,2 Astrid Wietelmann, 3 Himal Luitel, 1,2 Kirsten Murmann, 1,2 Damian Richard Krompiec, 1,2 Aleksandra Tretyn, 3 Soni Savai Pullamsetti, 3 Norbert Weissmann, 1,2 Werner Seeger, 1,2,3 Hossein Ardeschir Ghofrani, 1,2 and Ralph Theo Schermuly 1,2 1 Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany 2 German Center for Lung Research (DZL), 35392 Giessen, Germany 3 Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany Correspondence should be addressed to Ralph Teo Schermuly; ralph.schermuly@innere.med.uni-giessen.de Received 22 August 2014; Accepted 28 October 2014 Academic Editor: Shiro Mizuno Copyright © 2015 Wiebke Janssen et al. Tis 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. Objective. Te 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. Te aim of the current study was to investigate the efects 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 afer 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 fbroblasts isolated from RV tissues. Results. Chronic treatment with Terguride or SB204741 reduced right ventricular fbrosis and showed improved heart function in mice afer PAB. Moreover, 5-HT2B receptor antagonists diminished TGF-beta1 induced collagen synthesis of RV cardiac fbroblasts in vitro. Conclusion. 5-HT2B receptor antagonists reduce collagen deposition, thereby inhibiting right ventricular fbrosis. Chronic treatment prevented the development and progression of pressure overload-induced RVF in mice. Tus, 5-HT2B receptor antagonists represent a valuable novel therapeutic approach for RVF. 1. Introduction Sustained pressure overload of the right ventricle (RV) is a signifcant pathophysiological factor in several cardiovas- cular disorders, including pulmonary hypertension (PH). Outstandingly, RV failure (RVF) is the most common cause of death in patients with severe PH and is increasingly recognized as an important clinical problem [1, 2]. Long-term increase in pressure consequently results in RV hypertrophy (RVH). Initial cardiac hypertrophy can be considered as a benefcial response to changed hemodynamic parameters. During disease progression the maladaptive car- diac hypertrophy slowly proceeds to a decompensated state. With the progression of PH, the RV dilates, becomes fbrotic, and fnally undergoes functional failure, the ultimate cause of death in PH [3]. An accumulating body of evidence clearly underlines a signifcant role of 5-hydroxytryptamine (serotonin, 5-HT) in development and progression of LV hypertrophy (LVH) and fbrosis [4–6]. It was shown that serotonin, via the 5- HT2B receptor (5-HT2BR), regulates cardiac development and function [7, 8]. Also it was demonstrated that 5-HT2BR is essential for isoproterenol-induced cardiac hypertrophy, which is regulated by interleukin-6 (IL-6), interleukin-1 (IL- 1), and tumor necrosis factor  (TNF) cytokine production by cardiac fbroblasts [9]. Moreover, 5-HT2BR blockade has also been shown to prevent cardiac hypertrophy induced by angiotensin II or isoproterenol infusion [10]. In 2009, Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 438403, 8 pages http://dx.doi.org/10.1155/2015/438403