Prostaglandin and prostaglandin receptors: present and future promising therapeutic targets for pulmonary arterial hypertension.
Prostaglandin
Prostaglandin receptor
Pulmonary Hypertension
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
01 Nov 2023
01 Nov 2023
Historique:
received:
14
04
2023
accepted:
09
10
2023
medline:
3
11
2023
pubmed:
2
11
2023
entrez:
2
11
2023
Statut:
epublish
Résumé
Pulmonary arterial hypertension (PAH), Group 1 pulmonary hypertension (PH), is a type of pulmonary vascular disease characterized by abnormal contraction and remodeling of the pulmonary arterioles, manifested by pulmonary vascular resistance (PVR) and increased pulmonary arterial pressure, eventually leading to right heart failure or even death. The mechanisms involved in this process include inflammation, vascular matrix remodeling, endothelial cell apoptosis and proliferation, vasoconstriction, vascular smooth muscle cell proliferation and hypertrophy. In this study, we review the mechanisms of action of prostaglandins and their receptors in PAH. PAH-targeted therapies, such as endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, activators of soluble guanylate cyclase, prostacyclin, and prostacyclin analogs, improve PVR, mean pulmonary arterial pressure, and the six-minute walk distance, cardiac output and exercise capacity and are licensed for patients with PAH; however, they have not been shown to reduce mortality. Current treatments for PAH primarily focus on inhibiting excessive pulmonary vasoconstriction, however, vascular remodeling is recalcitrant to currently available therapies. Lung transplantation remains the definitive treatment for patients with PAH. Therefore, it is imperative to identify novel targets for improving pulmonary vascular remodeling in PAH. Studies have confirmed that prostaglandins and their receptors play important roles in the occurrence and development of PAH through vasoconstriction, vascular smooth muscle cell proliferation and migration, inflammation, and extracellular matrix remodeling. Prostacyclin and related drugs have been used in the clinical treatment of PAH. Other prostaglandins also have the potential to treat PAH. This review provides ideas for the treatment of PAH and the discovery of new drug targets.
Sections du résumé
BACKGROUND
BACKGROUND
Pulmonary arterial hypertension (PAH), Group 1 pulmonary hypertension (PH), is a type of pulmonary vascular disease characterized by abnormal contraction and remodeling of the pulmonary arterioles, manifested by pulmonary vascular resistance (PVR) and increased pulmonary arterial pressure, eventually leading to right heart failure or even death. The mechanisms involved in this process include inflammation, vascular matrix remodeling, endothelial cell apoptosis and proliferation, vasoconstriction, vascular smooth muscle cell proliferation and hypertrophy. In this study, we review the mechanisms of action of prostaglandins and their receptors in PAH.
MAIN BODY
METHODS
PAH-targeted therapies, such as endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, activators of soluble guanylate cyclase, prostacyclin, and prostacyclin analogs, improve PVR, mean pulmonary arterial pressure, and the six-minute walk distance, cardiac output and exercise capacity and are licensed for patients with PAH; however, they have not been shown to reduce mortality. Current treatments for PAH primarily focus on inhibiting excessive pulmonary vasoconstriction, however, vascular remodeling is recalcitrant to currently available therapies. Lung transplantation remains the definitive treatment for patients with PAH. Therefore, it is imperative to identify novel targets for improving pulmonary vascular remodeling in PAH. Studies have confirmed that prostaglandins and their receptors play important roles in the occurrence and development of PAH through vasoconstriction, vascular smooth muscle cell proliferation and migration, inflammation, and extracellular matrix remodeling.
CONCLUSION
CONCLUSIONS
Prostacyclin and related drugs have been used in the clinical treatment of PAH. Other prostaglandins also have the potential to treat PAH. This review provides ideas for the treatment of PAH and the discovery of new drug targets.
Identifiants
pubmed: 37915044
doi: 10.1186/s12931-023-02559-3
pii: 10.1186/s12931-023-02559-3
pmc: PMC10619262
doi:
Substances chimiques
Prostaglandins
0
Receptors, Prostaglandin
0
Epoprostenol
DCR9Z582X0
Prostaglandins I
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
263Subventions
Organisme : Fundamental Research Funds for Central Universities of the Central South University
ID : 2023ZZTS0877
Organisme : National Natural Science Foundation of China
ID : 82171557
Organisme : Natural Science Foundation of Hunan Province
ID : 2021JJ20085
Informations de copyright
© 2023. The Author(s).
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