New therapies in pulmonary arterial hypertension: Recent insights
Pulmonary Arterial Hypertension (PAH) is a complex and progressive disease characterized by elevated pulmonary vascular resistance and right heart failure. Current therapies primarily focus on pulmonary vasodilation; however, novel approaches that target the underlying pathophysiological mechanisms—...
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Elsevier
2025-03-01
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| Series: | International Journal of Cardiology Congenital Heart Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666668525000072 |
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| author | Giulia Guglielmi Konstantinos Dimopoulos S. John Wort |
| author_facet | Giulia Guglielmi Konstantinos Dimopoulos S. John Wort |
| author_sort | Giulia Guglielmi |
| collection | DOAJ |
| description | Pulmonary Arterial Hypertension (PAH) is a complex and progressive disease characterized by elevated pulmonary vascular resistance and right heart failure. Current therapies primarily focus on pulmonary vasodilation; however, novel approaches that target the underlying pathophysiological mechanisms—such as TGF-β signalling, epigenetic alterations, growth factors, inflammation, and extracellular matrix remodelling—are promising alternatives for improving treatment outcomes. This is a review of recent advances in the development of innovative therapeutic strategies for PAH.The first section of this paper explores approaches targeting TGF-β signalling, both acting directly on receptors through drugs like Sotatercept and exogenous BMP9, and indirectly, inhibiting the degradation of key receptors, such as BMPR2. Subsequent sections describe treatments that target epigenetic regulators, e.g. poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors and direct BRD4 antagonists, tyrosine kinase inhibitors (Seralutinib), and therapies aimed at inflammation, such as IL-6 inhibitors, CD-20 inhibitors, and monoclonal antibodies that prevent macrophage migration. Finally, strategies that target the serotonin pathway, and other metabolic and hormonal pathways are described.This review includes both preclinical and clinical trial data that support efficacy, safety and the future potential of such therapies. Collectively, these therapeutic approaches can be valuable in treating PAH by targeting multiple aspects of its pathogenesis, potentially resulting in improved clinical outcomes for patients affected by this debilitating, life-limiting condition. |
| format | Article |
| id | doaj-art-a9fcbeb5beab459c9c8b40989e74ad5c |
| institution | Kabale University |
| issn | 2666-6685 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Cardiology Congenital Heart Disease |
| spelling | doaj-art-a9fcbeb5beab459c9c8b40989e74ad5c2025-02-05T04:32:43ZengElsevierInternational Journal of Cardiology Congenital Heart Disease2666-66852025-03-0119100571New therapies in pulmonary arterial hypertension: Recent insightsGiulia Guglielmi0Konstantinos Dimopoulos1S. John Wort2Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, United KingdomAdult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, United Kingdom; National Pulmonary Hypertension Service, Royal Brompton Hospital, Imperial College London, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United KingdomNational Pulmonary Hypertension Service, Royal Brompton Hospital, Imperial College London, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; Corresponding author. Centre for Pulmonary Hypertension, Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust, Sydney Street, SW3 6NP, London, United Kingdom.S.Wort@rbht.nhs.ukPulmonary Arterial Hypertension (PAH) is a complex and progressive disease characterized by elevated pulmonary vascular resistance and right heart failure. Current therapies primarily focus on pulmonary vasodilation; however, novel approaches that target the underlying pathophysiological mechanisms—such as TGF-β signalling, epigenetic alterations, growth factors, inflammation, and extracellular matrix remodelling—are promising alternatives for improving treatment outcomes. This is a review of recent advances in the development of innovative therapeutic strategies for PAH.The first section of this paper explores approaches targeting TGF-β signalling, both acting directly on receptors through drugs like Sotatercept and exogenous BMP9, and indirectly, inhibiting the degradation of key receptors, such as BMPR2. Subsequent sections describe treatments that target epigenetic regulators, e.g. poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors and direct BRD4 antagonists, tyrosine kinase inhibitors (Seralutinib), and therapies aimed at inflammation, such as IL-6 inhibitors, CD-20 inhibitors, and monoclonal antibodies that prevent macrophage migration. Finally, strategies that target the serotonin pathway, and other metabolic and hormonal pathways are described.This review includes both preclinical and clinical trial data that support efficacy, safety and the future potential of such therapies. Collectively, these therapeutic approaches can be valuable in treating PAH by targeting multiple aspects of its pathogenesis, potentially resulting in improved clinical outcomes for patients affected by this debilitating, life-limiting condition.http://www.sciencedirect.com/science/article/pii/S2666668525000072Pulmonary arterial hypertension |
| spellingShingle | Giulia Guglielmi Konstantinos Dimopoulos S. John Wort New therapies in pulmonary arterial hypertension: Recent insights International Journal of Cardiology Congenital Heart Disease Pulmonary arterial hypertension |
| title | New therapies in pulmonary arterial hypertension: Recent insights |
| title_full | New therapies in pulmonary arterial hypertension: Recent insights |
| title_fullStr | New therapies in pulmonary arterial hypertension: Recent insights |
| title_full_unstemmed | New therapies in pulmonary arterial hypertension: Recent insights |
| title_short | New therapies in pulmonary arterial hypertension: Recent insights |
| title_sort | new therapies in pulmonary arterial hypertension recent insights |
| topic | Pulmonary arterial hypertension |
| url | http://www.sciencedirect.com/science/article/pii/S2666668525000072 |
| work_keys_str_mv | AT giuliaguglielmi newtherapiesinpulmonaryarterialhypertensionrecentinsights AT konstantinosdimopoulos newtherapiesinpulmonaryarterialhypertensionrecentinsights AT sjohnwort newtherapiesinpulmonaryarterialhypertensionrecentinsights |