Review
Cardiac & Cardiovascular Systems
Hui-ru Zhu, Hong-yu Kuang, Qiang Li, Xiao-juan Ji
Summary: Oral targeted treatments for PAH have been shown to decrease the risk of clinical worsening events, improve exercise capacity, and ameliorate functional class. Nitric oxide exhibits the most prominent clinical effect, but drugs targeting different pathways have applicability to different populations.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Wenxing Dong, Zhe Zhang, Mingming Chu, Peng Gu, Min Hu, Lulu Liu, Jingbin Huang, Rong Zhang
Summary: This study evaluated the cost-effectiveness of adding selexipag to the combined treatment of macitentan and tadalafil in patients with pulmonary arterial hypertension (PAH) in China. The results showed that adding selexipag increased costs but also improved quality-adjusted life years (QALYs), although the cost-effectiveness ratio was higher than the willingness-to-pay (WTP) threshold. The sensitivity analysis indicated that the results were most sensitive to mortality rates, discount rate, and the cost of selexipag.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Jigar Panchal, Shivangi Jaiswal, Sonika Jain, Jyoti Kumawat, Ashima Sharma, Pankaj Jain, Smita Jain, Kanika Verma, Jaya Dwivedi, Swapnil Sharma
Summary: Bosentan has limitations in clinical practices due to resistance, tolerance, and adverse effects. New derivatives, including 16h, show promising therapeutic efficacy and pharmacokinetic features as ET receptor antagonists in the management of PAH.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Christoph Tabeling, Carla Gonzalez R. Calera, Jasmin Lienau, Jakob Hoeppner, Thomas Tschernig, Olivia Kershaw, Birgitt Gutbier, Jan Naujoks, Julia Herbert, Bastian Opitz, Achim D. Gruber, Berthold Hocher, Norbert Suttorp, Harald Heidecke, Gerd-R. Burmester, Gabriela Riemekasten, Elise Siegert, Wolfgang M. Kuebler, Martin Witzenrath
Summary: This study provides evidence for the anti-inflammatory role of ETB and its protective effects on Th2-induced pathologies of the cardiovascular system. Autoantibodies against ETB may modulate ETB-mediated immune homeostasis.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Katsutoshi Tokushige, Tomomi Kogiso, Hiroto Egawa
Summary: Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome are severe pulmonary complications associated with liver cirrhosis (LC) and portal hypertension. Early diagnosis of PoPH and prompt initiation of therapy with PAH-specific drugs is important for achieving good treatment outcomes. Measurement of serum brain natriuretic peptide levels may be useful for detecting PoPH. Liver transplantation (LT) was previously contraindicated for PoPH, but the indications for LT are changing and now take into account how well the PoPH is controlled by therapeutic drugs.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Medicine, General & Internal
Nicole F. Ruopp, Barbara A. Cockrill
Summary: Pulmonary arterial hypertension, a subtype of pulmonary hypertension characterized by pulmonary arterial remodeling, can progress to right heart failure and death if left untreated. Approved therapies targeting multiple biological pathways have significantly improved survival rates.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Article
Cardiac & Cardiovascular Systems
Yong Dai, Zhihua Qiu, Wenrui Ma, Chang Li, Xiao Chen, Xiaoxiao Song, Zeyang Bai, Dingyang Shi, Jiayu Zheng, Guangwei Pan, Yuhua Liao, Mengyang Liao, Zihua Zhou
Summary: The study demonstrated that ETRQ beta-002 maintained immunological responses long-term, effectively reducing right ventricular systolic pressure and improving pulmonary arterial remodeling, while also exhibiting anti-proliferative, anti-inflammatory, and anti-fibrotic effects. Throughout the 21-week experiment, ETRQ beta-002 consistently limited pathological right ventricular hypertrophy and fibrosis, with no observed immune-mediated damage during long-term administration.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Review
Cardiac & Cardiovascular Systems
Matthias Gorenflo, Victoria C. Ziesenitz
Summary: Treatment of pediatric pulmonary arterial hypertension has advanced significantly, with new drug therapies being evaluated. Special attention is needed for the pharmacology of PAH drugs in children and more research is required.
CARDIOVASCULAR DIAGNOSIS AND THERAPY
(2021)
Review
Cardiac & Cardiovascular Systems
Fen Cao, Kun Wu, Yong-zhi Zhu, Jun-jun Jiang, Gui Zhang, Jun Liu, Ping Xiao, Yang Tian, Wei Zhang, Sheng Zhang, Feng Hou, Zhong-wu Bao
Summary: Based on the analysis of 27 randomized controlled trials, it was found that endothelin receptor antagonists (ERAs) were more effective than Prostaglandins (ProsA) in shortening the duration of mechanical ventilation, while ProsA were better than phosphodiesterase type 5 inhibitors (PDE-5i) in shortening the duration of mechanical ventilation and ICU stay. PDE-5i generated more benefits in decreasing the occurrence of pulmonary hypertension (PH) crisis.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Rheumatology
Oliver Distler, Christian Ofner, Doerte Huscher, Suzana Jordan, Silvia Ulrich, Gerd Staehler, Ekkehard Gruenig, Matthias Held, H. Ardeschir Ghofrani, Martin Claussen, Tobias J. Lange, Hans Klose, Stephan Rosenkranz, Anton Vonk-Noordegraaf, C. Dario Vizza, Marion Delcroix, Christian Opitz, Christine Pausch, Laura Scelsi, Claus Neurohr, Karen M. Olsson, J. Gerry Coghlan, Michael Halank, Dirk Skowasch, Juergen Behr, Katrin Milger, Bjoern Andrew Remppis, Andris Skride, Elena Jureviciene, Lina Gumbiene, Skaidrius Miliauskas, Judith Loeffler-Ragg, Heinrike Wilkens, David Pittrow, Marius M. Hoeper, Ralf Ewert
Summary: This study analyzed the treatment patterns and survival of patients with different connective tissue diseases (CTDs) associated with pulmonary arterial hypertension (PAH), finding that patients with SSc-PAH had the lowest survival rate. However, the study suggests that the combination therapy of endothelin receptor antagonists (ERAs) and phosphodiesterase type 5 inhibitors (PDE5is) may improve the long-term survival of patients with SSc-PAH.
Article
Pharmacology & Pharmacy
Yusi Chen, Jun Luo, Jingyuan Chen, Eugene Kotlyar, Zilu Li, Wenjie Chen, Jiang Li
Summary: The study on transitioning PAH patients from ambrisentan to macitentan showed successful and well-tolerated results, with improvements in exercise capacity, cardiac function, and hemodynamics. The transition was associated with greater efficacy and satisfaction.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Ronald Zolty
Summary: Pulmonary arterial hypertension (PAH) is characterized by distal pulmonary arterial remodeling and elevated pulmonary vascular resistance. Current approved vasodilator-specific therapy for PAH has shown significant improvement in functional capacity, quality of life, and invasive hemodynamics. However, there is still a need to identify new pathophysiologic signaling pathways.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Review
Biochemistry & Molecular Biology
Ruiqi Liu, Tianyi Yuan, Ranran Wang, Difei Gong, Shoubao Wang, Guanhua Du, Lianhua Fang
Summary: This paper reviews the regulation of endothelin receptors and their pathways in normal physiological processes and disease processes, and describes the mechanistic roles of ET receptor antagonists that are currently approved and used in clinical studies. Current clinical researches on ET are focused on the development of multi-target combinations and novel delivery methods to improve efficacy and patient compliance while reducing side effects. Future research directions and trends of ET targets, including monotherapy and precision medicine, are also described in this review.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yen-Yu Lu, Fong-Jhih Lin, Yao-Chang Chen, Yu-Hsun Kao, Satoshi Higa, Shih-Ann Chen, Yi-Jen Chen
Summary: Atrial arrhythmias in pulmonary arterial hypertension (PAH) are caused by atrial electrical and structural remodeling, with ET-1 levels correlating with disease severity. ET-1 acts as a trigger factor to initiate and maintain atrial arrhythmias in PAH by interacting with the arrhythmogenic substrate. The ET-1/ET-A receptor/ROCK signaling pathway may be a potential target for therapeutic interventions in PAH-induced atrial arrhythmias.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Zeyu Zhang, Chunlei Liu, Yongyi Bai, Xin Li, Xiaojian Gao, Chen Li, Ge Guo, Si Chen, Mingzhuang Sun, Kang Liu, Yang Li, Kunlun He
Summary: A novel endothelin receptor antagonist, pipersentan, has been synthesized and shown to effectively treat ET-1 system activation-related pulmonary arterial hypertension, making it a potential new therapeutic agent.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Evangelos D. Michelakis, Vikram Gurtu, Linda Webster, Gareth Barnes, Geoffrey Watson, Luke Howard, John Cupitt, Ian Paterson, Richard B. Thompson, Kelvin Chow, Declan P. O'Regan, Lan Zhao, John Wharton, David G. Kiely, Adam Kinnaird, Aristeidis E. Boukouris, Chris White, Jayan Nagendran, Darren H. Freed, Stephen J. Wort, J. Simon R. Gibbs, Martin R. Wilkins
SCIENCE TRANSLATIONAL MEDICINE
(2017)
Editorial Material
Respiratory System
Luke S. Howard
Article
Critical Care Medicine
Christopher J. Rhodes, John Wharton, Reinier A. Boon, Tino Roexe, Hilda Tsang, Beata Wojciak-Stothard, Anob Chakrabarti, Luke S. Howard, J. Simon R. Gibbs, Allan Lawrie, Robin Condliffes, Charles A. Elliot, David G. Kielys, Les Huson, Hossein A. Ghofrani, Henning Tiede, Ralph Schermuly, Andreas M. Zeihers, Stefanie Dimmeler, Martin R. Wilkins
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2013)
Article
Hematology
Ines Zimbarra Cabrita, Abubakar Mohammed, Mark Layton, Sara Ghorashian, Annette Gilmore, Gavin Cho, Jo Howard, Kofi A. Anie, Lynda Desforges, Paul Bassett, Julia Grapsa, Luke Howard, Gaia Mahalingam, David Dawson, Fausto J. Pinto, Petros Nihoyannopoulos, Sally C. Davies, J. Simon R. Gibbs
BRITISH JOURNAL OF HAEMATOLOGY
(2013)
Article
Cardiac & Cardiovascular Systems
Lan Zhao, Ali Ashek, Lei Wang, Wei Fang, Swati Dabral, Olivier Dubois, John Cupitt, Soni Savai Pullamsetti, Emanuele Cotroneo, Hazel Jones, Gianpaolo Tomasi, Quang-De Nguyen, Eric O. Aboagye, Mona A. El-Bahrawy, Gareth Barnes, Luke S. Howard, J. Simon R. Gibbs, Willy Gsell, Jian-Guo He, Martin R. Wilkins
Article
Cardiac & Cardiovascular Systems
Beata Wojciak-Stothard, Vahitha B. Abdul-Salam, Ka Hou Lao, Hilda Tsang, David C. Irwin, Christina Lisk, Zoe Loomis, Kurt R. Stenmark, John C. Edwards, Stuart H. Yuspa, Luke S. Howard, Robert J. Edwards, Christopher J. Rhodes, J. Simon R. Gibbs, John Wharton, Lan Zhao, Martin R. Wilkins
Letter
Respiratory System
B. R. O'Driscoll, A. Rudenski, P. M. Turkington, L. S. Howard
EUROPEAN RESPIRATORY JOURNAL
(2012)
Editorial Material
Respiratory System
Luke S. Howard
EUROPEAN RESPIRATORY JOURNAL
(2013)
Review
Cardiac & Cardiovascular Systems
Vallerie V. McLaughlin, Sean Patrick Gaine, Luke S. Howard, Hanno H. Leuchte, Michael A. Mathier, Sanjay Mehta, Massimillano Palazzini, Myung H. Park, Victor F. Tapson, Olivier Sitbon
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2013)
Article
Rheumatology
Gerrina Ruiter, Irene J. Lanser, Frances S. de Man, Willem J. van der Laarse, John Wharton, Martin R. Wilkins, Luke S. Howard, Anton Vonk-Noordegraaf, Alexandre E. Voskuyl
Article
Respiratory System
Luke S. Howard, Rodney J. Hughes
Letter
Respiratory System
Dinesh Shrikrishna, Luke Howard, Robina K. Coker
Editorial Material
Respiratory System
Luke S. Howard
Review
Respiratory System
Loic Guillevin, Iain Armstrong, Rino Aldrighetti, Luke S. Howard, Henrik Ryftenius, Aryeh Fischer, Sandra Lombardi, Sean Studer, Pisana Ferrari
EUROPEAN RESPIRATORY REVIEW
(2013)
Review
Respiratory System
Luke S. Howard, Julia Grapsa, David Dawson, Michael Bellamy, John B. Chambers, Navroz D. Masani, Petros Nihoyannopoulos, J. Simon R. Gibbs
EUROPEAN RESPIRATORY REVIEW
(2012)