Thomas Beiert1, Vedat Tiyerili2, Vincent Knappe2, Verena Effelsberg2, Markus Linhart2, Florian Stöckigt2, Sabine Klein3, Robert Schierwagen3, Jonel Trebicka4, Georg Nickenig2, Jan W Schrickel2, René P Andrié2. 1. Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany. Electronic address: Thomas.Beiert@ukbonn.de. 2. Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany. 3. Department of Internal Medicine I, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany. 4. Department of Internal Medicine I, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; European Foundation for the Study of Chronic Liver Failure - EF Clif, Barcelona, Spain; Institute for Bioengineering of Catalonia, Barcelona, Spain.
Abstract
BACKGROUND: Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI). METHODS: Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 μg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps. RESULTS: RLX treatment significantly attenuated the increase in AF-inducibility following cryoinfarction and reduced the mean duration of AF episodes. Furthermore, epicardial mapping of both atria revealed an increase in conduction velocity. In addition to an attenuation of atrial hypertrophy, chronic application of RLX reduced atrial fibrosis, which was linked to a significant reduction in atrial mRNA expression of connective tissue growth factor. Transcript levels of the pro-inflammatory cytokines interleukin-6 and interleukin-1β were reduced in RLX treated mice, but macrophage infiltration into atrial myocardium was similar in the vehicle and RLX treated groups. CONCLUSION: Treatment with RLX in mice after MI reduces susceptibility to AF due to anti-inflammatory and anti-fibrotic properties. Because to these favorable actions, RLX may become a new therapeutic option in the treatment of AF, even when complicating MI.
BACKGROUND:Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI). METHODS:Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 μg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps. RESULTS: RLX treatment significantly attenuated the increase in AF-inducibility following cryoinfarction and reduced the mean duration of AF episodes. Furthermore, epicardial mapping of both atria revealed an increase in conduction velocity. In addition to an attenuation of atrial hypertrophy, chronic application of RLX reduced atrial fibrosis, which was linked to a significant reduction in atrial mRNA expression of connective tissue growth factor. Transcript levels of the pro-inflammatory cytokines interleukin-6 and interleukin-1β were reduced in RLX treated mice, but macrophage infiltration into atrial myocardium was similar in the vehicle and RLX treated groups. CONCLUSION: Treatment with RLX in mice after MI reduces susceptibility to AF due to anti-inflammatory and anti-fibrotic properties. Because to these favorable actions, RLX may become a new therapeutic option in the treatment of AF, even when complicating MI.
Authors: Sandra Feijóo-Bandín; Alana Aragón-Herrera; Diego Rodríguez-Penas; Manuel Portolés; Esther Roselló-Lletí; Miguel Rivera; José R González-Juanatey; Francisca Lago Journal: Front Physiol Date: 2017-08-18 Impact factor: 4.566
Authors: Julian A Luetkens; Anne C Wolpers; Thomas Beiert; Daniel Kuetting; Darius Dabir; Rami Homsi; Hendrik Meendermann; Natalie Abou Dayé; Vincent Knappe; Morten Karsdal; Signe H Nielsen; Federica Genovese; Florian Stöckigt; Markus Linhart; Daniel Thomas; Georg Nickenig; Hans H Schild; Jan W Schrickel; René P Andrié Journal: Sci Rep Date: 2018-09-11 Impact factor: 4.379