TY - JOUR T1 - Riociguat for treatment of pulmonary hypertension in COPD: a translational study JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.02445-2018 VL - 53 IS - 6 SP - 1802445 AU - Alexandra Pichl AU - Natascha Sommer AU - Mariola Bednorz AU - Michael Seimetz AU - Stefan Hadzic AU - Stefan Kuhnert AU - Simone Kraut AU - Elsa T. Roxlau AU - Baktybek Kojonazarov AU - Jochen Wilhelm AU - Marija Gredic AU - Henning Gall AU - Khodr Tello AU - Manuel J. Richter AU - Oleg Pak AU - Aleksandar Petrovic AU - Matthias Hecker AU - Ralph T. Schermuly AU - Friedrich Grimminger AU - Werner Seeger AU - Hossein A. Ghofrani AU - Norbert Weissmann Y1 - 2019/06/01 UR - http://erj.ersjournals.com/content/53/6/1802445.abstract N2 - Chronic obstructive pulmonary disease (COPD), which comprises the phenotypes of chronic bronchitis and emphysema, is often associated with pulmonary hypertension (PH). However, currently, no approved therapy exists for PH-COPD. Signalling of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) axis plays an important role in PH and COPD.We investigated the treatment effect of riociguat, which promotes the NO–cGMP pathway, in the mouse model of smoke-induced PH and emphysema in a curative approach, and retrospectively analysed the effect of riociguat treatment on PH in single patients with PH-COPD.In mice with established PH and emphysema (after 8 months of cigarette smoke exposure), riociguat treatment for another 3 months fully reversed PH. Moreover, histological hallmarks of emphysema were decreased. Microarray analysis revealed involvement of different signalling pathways, e.g. related to matrix metalloproteinases (MMPs). MMP activity was decreased in vivo by riociguat. In PH-COPD patients treated with riociguat (n=7), the pulmonary vascular resistance, airway resistance and circulating MMP levels decreased, while oxygenation at rest was not significantly changed.Riociguat may be beneficial for treatment of PH-COPD. Further long-term prospective studies are necessary to investigate the tolerability, efficacy on functional parameters and effect specifically on pulmonary emphysema in COPD patients.The soluble guanylate cyclase stimulator riociguat reverses fully established cigarette smoke-induced pulmonary emphysema and hypertension in mice, and may have beneficial effects on PH in patients presenting with both PH and moderate COPD http://ow.ly/dGgL30oj7LC ER -