Sommer Natascha, Ghofrani Hossein A, Pak Oleg, Bonnet Sebastien, Provencher Steve, Sitbon Olivier, Rosenkranz Stephan, Hoeper Marius M, Kiely David G
Cardiopulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig-University, Giessen, Germany.
Department of Medicine, Imperial College London, London, UK.
Br J Pharmacol. 2021 Jan;178(1):6-30. doi: 10.1111/bph.15016. Epub 2020 Mar 23.
Therapeutic options for pulmonary arterial hypertension (PAH) have increased over the last decades. The advent of pharmacological therapies targeting the prostacyclin, endothelin, and NO pathways has significantly improved outcomes. However, for the vast majority of patients, PAH remains a life-limiting illness with no prospect of cure. PAH is characterised by pulmonary vascular remodelling. Current research focusses on targeting the underlying pathways of aberrant proliferation, migration, and apoptosis. Despite success in preclinical models, using a plethora of novel approaches targeting cellular GPCRs, ion channels, metabolism, epigenetics, growth factor receptors, transcription factors, and inflammation, successful transfer to human disease with positive outcomes in clinical trials is limited. This review provides an overview of novel targets addressed by clinical trials and gives an outlook on novel preclinical perspectives in PAH. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.
在过去几十年中，肺动脉高压（PAH）的治疗选择有所增加。针对前列环素、内皮素和一氧化氮途径的药物治疗的出现显著改善了治疗效果。然而，对于绝大多数患者来说，PAH仍然是一种危及生命的疾病，没有治愈的希望。PAH的特征是肺血管重塑。目前的研究集中在针对异常增殖、迁移和凋亡的潜在途径。尽管在临床前模型中取得了成功，使用了大量针对细胞GPCR、离子通道、代谢、表观遗传学、生长因子受体、转录因子和炎症的新方法，但在临床试验中成功转化为人类疾病并取得积极结果的情况有限。本综述概述了临床试验中涉及的新靶点，并展望了PAH新的临床前研究前景。相关文章：本文是关于心脏保护中的危险因素、合并症和联合用药的主题问题的一部分。要查看本节中的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc。
