The Potential Application and Promising Role of Targeted Therapy in Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a rare yet serious progressive disorder that is currently incurable. This female-predominant disease unfolds as a pan-vasculopathy that affects all layers of the vessel wall. Five classes of pharmacological agents currently exist to target the three major cel...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/6/1415 |
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| author | Meng-Chien Willie Hsieh Wei-Ting Wang Jwu-Lai Yeh Chuang-Yu Lin Yur-Ren Kuo Su-Shin Lee Ming-Feng Hou Yi-Chia Wu |
| author_facet | Meng-Chien Willie Hsieh Wei-Ting Wang Jwu-Lai Yeh Chuang-Yu Lin Yur-Ren Kuo Su-Shin Lee Ming-Feng Hou Yi-Chia Wu |
| author_sort | Meng-Chien Willie Hsieh |
| collection | DOAJ |
| description | Pulmonary arterial hypertension (PAH) is a rare yet serious progressive disorder that is currently incurable. This female-predominant disease unfolds as a pan-vasculopathy that affects all layers of the vessel wall. Five classes of pharmacological agents currently exist to target the three major cellular signaling pathways identified in PAH but are incapable of effectively reversing the disease progression. While several targets have been identified for therapy, none of the current PAH specific therapies are curative and cost-effective as they fail to reverse vascular remodeling and do not address the cancer-like features of PAH. Our purpose is to review the current literature on the therapeutic management of PAH, as well as the molecular targets under consideration for therapy so as to shed light on the potential role and future promise of novel strategies in treating this high-mortality disease. This review study summarizes and discusses the potential therapeutic targets to be employed against PAH. In addition to the three major conventional pathways already used in PAH therapy, targeting PDGF/PDGFR signaling, regulators in glycolytic metabolism, PI3K/AKT pathways, mitochondrial heat shock protein 90 (HSP90), high-mobility group box-1 (HMGB1), and bromodomain and extra-terminal (BET) proteins by using their specific inhibitors, or a pharmacological induction of the p53 expression, could be attractive strategies for treating PAH. |
| first_indexed | 2024-03-10T00:19:48Z |
| format | Article |
| id | doaj.art-6064ea0dcf4340cd84b2403317792825 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:19:48Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-6064ea0dcf4340cd84b24033177928252023-11-23T15:44:25ZengMDPI AGBiomedicines2227-90592022-06-01106141510.3390/biomedicines10061415The Potential Application and Promising Role of Targeted Therapy in Pulmonary Arterial HypertensionMeng-Chien Willie Hsieh0Wei-Ting Wang1Jwu-Lai Yeh2Chuang-Yu Lin3Yur-Ren Kuo4Su-Shin Lee5Ming-Feng Hou6Yi-Chia Wu7Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanDivision of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanDepartment of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDivision of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanDivision of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanDepartment of Surgery, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDivision of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanPulmonary arterial hypertension (PAH) is a rare yet serious progressive disorder that is currently incurable. This female-predominant disease unfolds as a pan-vasculopathy that affects all layers of the vessel wall. Five classes of pharmacological agents currently exist to target the three major cellular signaling pathways identified in PAH but are incapable of effectively reversing the disease progression. While several targets have been identified for therapy, none of the current PAH specific therapies are curative and cost-effective as they fail to reverse vascular remodeling and do not address the cancer-like features of PAH. Our purpose is to review the current literature on the therapeutic management of PAH, as well as the molecular targets under consideration for therapy so as to shed light on the potential role and future promise of novel strategies in treating this high-mortality disease. This review study summarizes and discusses the potential therapeutic targets to be employed against PAH. In addition to the three major conventional pathways already used in PAH therapy, targeting PDGF/PDGFR signaling, regulators in glycolytic metabolism, PI3K/AKT pathways, mitochondrial heat shock protein 90 (HSP90), high-mobility group box-1 (HMGB1), and bromodomain and extra-terminal (BET) proteins by using their specific inhibitors, or a pharmacological induction of the p53 expression, could be attractive strategies for treating PAH.https://www.mdpi.com/2227-9059/10/6/1415pulmonary arterial hypertensionmolecular base pathophysiologytargeted therapyWarburg Effect |
| spellingShingle | Meng-Chien Willie Hsieh Wei-Ting Wang Jwu-Lai Yeh Chuang-Yu Lin Yur-Ren Kuo Su-Shin Lee Ming-Feng Hou Yi-Chia Wu The Potential Application and Promising Role of Targeted Therapy in Pulmonary Arterial Hypertension Biomedicines pulmonary arterial hypertension molecular base pathophysiology targeted therapy Warburg Effect |
| title | The Potential Application and Promising Role of Targeted Therapy in Pulmonary Arterial Hypertension |
| title_full | The Potential Application and Promising Role of Targeted Therapy in Pulmonary Arterial Hypertension |
| title_fullStr | The Potential Application and Promising Role of Targeted Therapy in Pulmonary Arterial Hypertension |
| title_full_unstemmed | The Potential Application and Promising Role of Targeted Therapy in Pulmonary Arterial Hypertension |
| title_short | The Potential Application and Promising Role of Targeted Therapy in Pulmonary Arterial Hypertension |
| title_sort | potential application and promising role of targeted therapy in pulmonary arterial hypertension |
| topic | pulmonary arterial hypertension molecular base pathophysiology targeted therapy Warburg Effect |
| url | https://www.mdpi.com/2227-9059/10/6/1415 |
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