{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T07:16:36Z","timestamp":1776496596823,"version":"3.51.2"},"reference-count":35,"publisher":"European Respiratory Society (ERS)","issue":"6","license":[{"start":{"date-parts":[[2019,4,7]],"date-time":"2019-04-07T00:00:00Z","timestamp":1554595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.ersjournals.com\/user-licence"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1213 Project A07, Project CP02"],"award-info":[{"award-number":["SFB1213 Project A07, Project CP02"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2019,3,26]]},"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>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)\u2013cyclic guanosine monophosphate (cGMP) axis plays an important role in PH and COPD.<\/jats:p><jats:p>We investigated the treatment effect of riociguat, which promotes the NO\u2013cGMP 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.<\/jats:p><jats:p>In mice with established PH and emphysema (after 8\u2005months of cigarette smoke exposure), riociguat treatment for another 3\u2005months fully reversed PH. Moreover, histological hallmarks of emphysema were decreased. Microarray analysis revealed involvement of different signalling pathways,<jats:italic>e.g.<\/jats:italic>related to matrix metalloproteinases (MMPs). MMP activity was decreased<jats:italic>in vivo<\/jats:italic>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.<\/jats:p><jats:p>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.<\/jats:p>","DOI":"10.1183\/13993003.02445-2018","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T04:24:12Z","timestamp":1554697452000},"page":"1802445","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Riociguat for treatment of pulmonary hypertension in COPD: a translational study"],"prefix":"10.1183","volume":"53","author":[{"given":"Alexandra","family":"Pichl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natascha","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariola","family":"Bednorz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Seimetz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Hadzic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Kuhnert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Kraut","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elsa T.","family":"Roxlau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baktybek","family":"Kojonazarov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Wilhelm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Gredic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7016-7373","authenticated-orcid":false,"given":"Henning","family":"Gall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khodr","family":"Tello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel J.","family":"Richter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleg","family":"Pak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandar","family":"Petrovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Hecker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph T.","family":"Schermuly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friedrich","family":"Grimminger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1946-0894","authenticated-orcid":false,"given":"Werner","family":"Seeger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hossein A.","family":"Ghofrani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Weissmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"81","published-online":{"date-parts":[[2019,4,7]]},"reference":[{"key":"2024102100550562000_53.6.1802445.1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201204-0596PP"},{"key":"2024102100550562000_53.6.1802445.2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-0820"},{"key":"2024102100550562000_53.6.1802445.3","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01032-2015"},{"key":"2024102100550562000_53.6.1802445.4","doi-asserted-by":"crossref","first-page":"39s","DOI":"10.1378\/chest.10-0087","article-title":"Pulmonary hypertension in COPD: epidemiology, significance, and management: pulmonary vascular disease: the global perspective","volume":"137","author":"Minai","year":"2010","journal-title":"Chest"},{"key":"2024102100550562000_53.6.1802445.5","first-page":"S57","article-title":"Pulmonale Hypertonie bei Lungenkrankheiten: Empfehlungen der Kolner Konsensus-Konferenz 2016. [Pulmonary hypertension due to chronic lung disease: recommendations of the Cologne Consensus Conference 2016.]","volume":"141","author":"Olschewski","year":"2016","journal-title":"Dtsch Med Wochenschr"},{"key":"2024102100550562000_53.6.1802445.6","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.healun.2016.04.010","article-title":"Sildenafil in severe pulmonary hypertension associated with chronic obstructive pulmonary disease: a randomized controlled multicenter clinical trial","volume":"36","author":"Vitulo","year":"2017","journal-title":"J Heart Lung Transplant"},{"key":"2024102100550562000_53.6.1802445.7","first-page":"81","article-title":"Sildenafil improves six-minute walk distance in chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial","volume":"53","author":"Rao","year":"2011","journal-title":"Indian J Chest Dis Allied Sci"},{"key":"2024102100550562000_53.6.1802445.8","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00176312"},{"key":"2024102100550562000_53.6.1802445.9","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201311-2037OC"},{"key":"2024102100550562000_53.6.1802445.10","doi-asserted-by":"crossref","first-page":"e0129327","DOI":"10.1371\/journal.pone.0129327","article-title":"Cigarette smoke-induced emphysema and pulmonary hypertension can be prevented by phosphodiesterase 4 and 5 inhibition in mice","volume":"10","author":"Seimetz","year":"2015","journal-title":"PLoS One"},{"key":"2024102100550562000_53.6.1802445.11","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00139914"},{"key":"2024102100550562000_53.6.1802445.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.035"},{"key":"2024102100550562000_53.6.1802445.13","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai9048"},{"key":"2024102100550562000_53.6.1802445.14","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01941-2015"},{"key":"2024102100550562000_53.6.1802445.15","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.healun.2017.02.016","article-title":"The Giessen Pulmonary Hypertension Registry: survival in pulmonary hypertension subgroups","volume":"36","author":"Gall","year":"2017","journal-title":"J Heart Lung Transplant"},{"key":"2024102100550562000_53.6.1802445.16","doi-asserted-by":"publisher","DOI":"10.1038\/5096"},{"key":"2024102100550562000_53.6.1802445.17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pmbts.2017.04.004","article-title":"The role of matrix metalloproteinases in development, repair, and destruction of the lungs","volume":"148","author":"Hendrix","year":"2017","journal-title":"Prog Mol Biol Transl Sci"},{"key":"2024102100550562000_53.6.1802445.18","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s00005-015-0375-5","article-title":"Matrix metalloproteinases and their inhibitors in chronic obstructive pulmonary disease","volume":"64","author":"Navratilova","year":"2016","journal-title":"Arch Immunol Ther Exp"},{"key":"2024102100550562000_53.6.1802445.19","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00209911"},{"key":"2024102100550562000_53.6.1802445.20","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.bbamcr.2013.12.006","article-title":"Nitric oxide-matrix metaloproteinase-9 interactions: biological and pharmacological significance: NO and MMP-9 interactions","volume":"1843","author":"O'Sullivan","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"2024102100550562000_53.6.1802445.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0304264101"},{"key":"2024102100550562000_53.6.1802445.22","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr304"},{"key":"2024102100550562000_53.6.1802445.23","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.rmed.2015.05.022","article-title":"Lung function in pulmonary hypertension","volume":"109","author":"Low","year":"2015","journal-title":"Respir Med"},{"key":"2024102100550562000_53.6.1802445.24","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.57.6.473"},{"key":"2024102100550562000_53.6.1802445.25","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1513\/AnnalsATS.201601-048LE","article-title":"Impaired respiratory function in chronic thromboembolic pulmonary hypertension: a comparative study with healthy control subjects","volume":"13","author":"Fukushi","year":"2016","journal-title":"Ann Am Thorac Soc"},{"key":"2024102100550562000_53.6.1802445.26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209657"},{"key":"2024102100550562000_53.6.1802445.27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209655"},{"key":"2024102100550562000_53.6.1802445.28","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.healun.2016.12.012","article-title":"Comparison of hemodynamic parameters in treatment-naive and pre-treated patients with pulmonary arterial hypertension in the randomized phase III PATENT-1 study","volume":"36","author":"Galie","year":"2017","journal-title":"J Heart Lung Transplant"},{"key":"2024102100550562000_53.6.1802445.29","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1086\/680214","article-title":"Acute effects of riociguat in borderline or manifest pulmonary hypertension associated with chronic obstructive pulmonary disease","volume":"5","author":"Ghofrani","year":"2015","journal-title":"Pulm Circ"},{"key":"2024102100550562000_53.6.1802445.30","first-page":"199","article-title":"Hypoxemia in patients with COPD: cause, effects, and disease progression","volume":"6","author":"Kent","year":"2011","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"2024102100550562000_53.6.1802445.31","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00007913"},{"key":"2024102100550562000_53.6.1802445.32","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201408-1423OC"},{"key":"2024102100550562000_53.6.1802445.33","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201508-1647OC"},{"key":"2024102100550562000_53.6.1802445.34","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.001458"},{"key":"2024102100550562000_53.6.1802445.35","doi-asserted-by":"publisher","DOI":"10.1159\/000350451"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.02445-2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T07:37:41Z","timestamp":1740382661000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.02445-2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,7]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,6,27]]},"published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1183\/13993003.02445-2018"],"URL":"https:\/\/doi.org\/10.1183\/13993003.02445-2018","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,7]]}}}