PT - JOURNAL ARTICLE AU - Clara Dees AU - Christian Beyer AU - Alfiya Distler AU - Alina Soare AU - Yun Zhang AU - Katrin Palumbo-Zerr AU - Oliver Distler AU - Georg Schett AU - Peter Sandner AU - Jörg H W Distler TI - Stimulators of soluble guanylate cyclase (sGC) inhibit experimental skin fibrosis of different aetiologies AID - 10.1136/annrheumdis-2014-206809 DP - 2015 Aug 01 TA - Annals of the Rheumatic Diseases PG - 1621--1625 VI - 74 IP - 8 4099 - http://ard.bmj.com/content/74/8/1621.short 4100 - http://ard.bmj.com/content/74/8/1621.full SO - Ann Rheum Dis2015 Aug 01; 74 AB - Objectives Stimulators of the soluble guanylate cyclase (sGC) have recently been shown to inhibit transforming growth factor-β signalling. Here, we aimed to demonstrate that riociguat, the drug candidate for clinical trials in systemic sclerosis (SSc), is effective in experimental fibrosis and to compare its efficacy to that of phosphodiesterase V inhibitors that also increase the intracellular levels of cyclic guanosine monophosphate.Methods The antifibrotic effects of riociguat and sildenafil were compared in the tight-skin 1 model, in bleomycin-induced fibrosis and in a model of sclerodermatous chronic graft-versus-host-disease (cGvHD). Doses of 0.1–3 mg/kg twice a day for riociguat and of 3–10 mg/kg twice a day for sildenafil were used.Result Riociguat dose-dependently reduced skin thickening, myofibroblast differentiation and accumulation of collagen with potent antifibrotic effects at 1 and 3 mg/kg. Riociguat also ameliorated fibrosis of the gastrointestinal tract in the cGvHD model. The antifibrotic effects were associated with reduced phosphorylation of extracellular signal-regulated kinases. Sildenafil at doses of 3 and 10 mg/kg exerted mild antifibrotic effects that were significantly less pronounced compared with 1 and 3 mg/kg riociguat.Conclusions These data demonstrated potent antifibrotic effects of riociguat on experimental skin and organ fibrosis. These findings suggest a role for riociguat for the treatment of fibrotic diseases, especially for the treatment of SSc. A phase II study with riociguat in patients with SSc is currently starting.