Excellence Cluster Cardiopulmonary System, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University, Giessen, Germany.
These two authors contributed equally to this work.
Eur Respir J. 2019 Jun 27;53(6). doi: 10.1183/13993003.02445-2018. Print 2019 Jun.
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, related to matrix metalloproteinases (MMPs). MMP activity was decreased 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.
慢性阻塞性肺疾病（COPD）包括慢性支气管炎和肺气肿两种表型，常伴有肺动脉高压（PH）。然而，目前尚无针对 PH-COPD 的获批治疗方法。一氧化氮（NO）-环鸟苷酸（cGMP）轴的信号转导在 PH 和 COPD 中起着重要作用。我们研究了促进 NO-cGMP 通路的 riociguat 在烟雾诱导的 PH 和肺气肿小鼠模型中的治疗效果，以及回顾性分析 riociguat 治疗对单个 PH-COPD 患者 PH 的影响。在已经建立 PH 和肺气肿的小鼠（在吸烟暴露 8 个月后）中，riociguat 治疗另外 3 个月可完全逆转 PH。此外，肺气肿的组织学特征减少。微阵列分析显示涉及不同的信号通路，与基质金属蛋白酶（MMPs）有关。riociguat 降低了 MMP 活性。在接受 riociguat 治疗的 PH-COPD 患者（n=7）中，肺血管阻力、气道阻力和循环 MMP 水平降低，而静息时的氧合作用没有明显变化。Riociguat 可能有益于治疗 PH-COPD。需要进一步进行长期前瞻性研究，以调查 riociguat 在 COPD 患者中的耐受性、对功能参数的疗效以及对肺气肿的特异性影响。
