Experimental animal models and patient-derived platforms to bridge preclinical discovery and translational therapeutics in pulmonary arterial hypertension

Abstract Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by sustained elevation of pulmonary arterial pressure, endothelial cell dysfunction, and right ventricular failure. A wide range of experimental animal models, including the monocrotaline model, Sugen comb...

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Main Authors: Elizabeth Singh, Malik Bisserier
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-025-06709-7
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author Elizabeth Singh
Malik Bisserier
author_facet Elizabeth Singh
Malik Bisserier
author_sort Elizabeth Singh
collection DOAJ
description Abstract Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by sustained elevation of pulmonary arterial pressure, endothelial cell dysfunction, and right ventricular failure. A wide range of experimental animal models, including the monocrotaline model, Sugen combined with hypoxia, and pulmonary artery banding in large animals, have been pivotal in uncovering disease mechanisms such as vascular remodeling, metabolic dysregulation, and hypoxia-inducible signaling. More recently, human-based platforms, including induced pluripotent stem cell-derived vascular cells, organ-on-chip systems, and precision-cut lung slices, have emerged as powerful tools to model patient-specific pathophysiology and study pharmacological responses. These systems enable the interrogation of BMPR2 mutations, mitochondrial dysfunction, and sex-specific responses, factors often overlooked in traditional preclinical models. Moreover, integrating these platforms with omics technologies and comorbidity-driven experimental systems addresses key translational gaps. This review provides an overview of animal and human-based models used in PAH research and highlights emerging strategies to enhance their translational relevance. We advocate for a multi-platform and precision medicine-oriented approach that bridges preclinical insights with clinical outcomes to accelerate therapeutic development in PAH.
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spelling doaj-art-2a5f85d79d344cd48842cf134ad972c12025-08-20T02:37:35ZengBMCJournal of Translational Medicine1479-58762025-06-0123111610.1186/s12967-025-06709-7Experimental animal models and patient-derived platforms to bridge preclinical discovery and translational therapeutics in pulmonary arterial hypertensionElizabeth Singh0Malik Bisserier1Department of Cell Biology and Anatomy, New York Medical CollegeDepartment of Cell Biology and Anatomy, New York Medical CollegeAbstract Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by sustained elevation of pulmonary arterial pressure, endothelial cell dysfunction, and right ventricular failure. A wide range of experimental animal models, including the monocrotaline model, Sugen combined with hypoxia, and pulmonary artery banding in large animals, have been pivotal in uncovering disease mechanisms such as vascular remodeling, metabolic dysregulation, and hypoxia-inducible signaling. More recently, human-based platforms, including induced pluripotent stem cell-derived vascular cells, organ-on-chip systems, and precision-cut lung slices, have emerged as powerful tools to model patient-specific pathophysiology and study pharmacological responses. These systems enable the interrogation of BMPR2 mutations, mitochondrial dysfunction, and sex-specific responses, factors often overlooked in traditional preclinical models. Moreover, integrating these platforms with omics technologies and comorbidity-driven experimental systems addresses key translational gaps. This review provides an overview of animal and human-based models used in PAH research and highlights emerging strategies to enhance their translational relevance. We advocate for a multi-platform and precision medicine-oriented approach that bridges preclinical insights with clinical outcomes to accelerate therapeutic development in PAH.https://doi.org/10.1186/s12967-025-06709-7Pulmonary hypertensionPreclinical modelsTranslational approachesAnimal modelsPatient-derived systemsBiomarkers
spellingShingle Elizabeth Singh
Malik Bisserier
Experimental animal models and patient-derived platforms to bridge preclinical discovery and translational therapeutics in pulmonary arterial hypertension
Journal of Translational Medicine
Pulmonary hypertension
Preclinical models
Translational approaches
Animal models
Patient-derived systems
Biomarkers
title Experimental animal models and patient-derived platforms to bridge preclinical discovery and translational therapeutics in pulmonary arterial hypertension
title_full Experimental animal models and patient-derived platforms to bridge preclinical discovery and translational therapeutics in pulmonary arterial hypertension
title_fullStr Experimental animal models and patient-derived platforms to bridge preclinical discovery and translational therapeutics in pulmonary arterial hypertension
title_full_unstemmed Experimental animal models and patient-derived platforms to bridge preclinical discovery and translational therapeutics in pulmonary arterial hypertension
title_short Experimental animal models and patient-derived platforms to bridge preclinical discovery and translational therapeutics in pulmonary arterial hypertension
title_sort experimental animal models and patient derived platforms to bridge preclinical discovery and translational therapeutics in pulmonary arterial hypertension
topic Pulmonary hypertension
Preclinical models
Translational approaches
Animal models
Patient-derived systems
Biomarkers
url https://doi.org/10.1186/s12967-025-06709-7
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