Abstract 217: Anti-fibrotic Function of Relaxin

Abstract

Introduction: The RELAX in Acute Heart Failure (RELAX-AHF) trial was done in patients admitted for acute decompensated heart failure to evaluate the efficacy of Serelaxin (human recombinant relaxin-2) on dyspnoea relief, as well as its safety and tolerability. Interestingly, the 180-day mortality was significantly better in the Serelaxin group compared to placebo. The pathophysiology of these beneficial effects remains elusive. Methods and results: To induce heart failure in mice, they were treated with Angiotensin II in absence or in presence of relaxin. After 21 days hemodynamic measurements revealed an improved hemodynamic function in relaxin treated animals with AngII-induced heart failure compared to mice without relaxin treatment. To further investigate the , cardiac fibroblasts were stimulated with pro-fibrotic TGF-β in the presence or in the absence of relaxin. Additionally as a control cardiac fibroblasts were treated with relaxin alone. The treatment with TGF-β induced an increased gene expression of connective tissue growth factor (CTGF) as well as monocyte chemotactic protein 1 (MCP-1) in cardiac fibroblasts, whereas treatment with relaxin alone decreased the gene expression level of CTGF as well as MCP-1 . To investigate a potential inhibitory function of relaxin during TGF-β induced pro-fibrotic gene expression regulation, cardiac fibroblasts were pre-incubated with relaxin 1 hour prior to TGF-β treatment. After the following 6 hours of TGF-β treatment no decreased gene expression was observed in relaxin pre-treated cardiac fibroblasts compared to TGF-β stimulated fibroblasts without relaxin treatment. Conclusion: In this study we could demonstrate no inhibitory effect of relaxin during the pro-fibrotic TGF-β-induced signaling pathway. Nevertheless, relaxin alone induced anti-fibrotic function. Therefore, we conclude that the anti-fibrotic function is not due to an influence on the TGF-β induced pro-fibrotic signaling.