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

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.