Lan Zhao, Christine M. Cunningham, Jason Hong, Stuti Agarwal, Ke Yuan, Vinicio A. de Jesus Perez, Mark R. Nicolls
Stanford University. University of California, Los Angeles. Boston Children’s Hospital.
United States
American Journal of Respiratory Cell and Molecular Biology
Am J Respir Cell Mol Biol 2025;
DOI: 10.1165/rcmb.2024-0410OC
Abstract
Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling and right ventricle (RV) dysfunction. Among the five PH groups, group 1 pulmonary arterial hypertension (PAH) is a particularly serious condition characterized by a poor prognosis. PAH can be in idiopathic (IPAH), associated (APAH), and heritable (HPAH) forms, and has a notable female predominance. A number of in vivo PH models in rodents together with in vitro cultured vascular cells such as pulmonary arterial endothelial cells (PAECs) and pulmonary arterial smooth muscle cells (PASMCs) derived from PAH patients have been widely used to reproduce the pathological disease features. To systematically evaluate the in vivo and in vitro efficacy of the existing PH model systems, publicly available whole transcriptome data from both humans and rodents were collected and analyzed. Subgroups of Schistosoma-induced female PH in mice and male chronic hypoxia (CH)-PH model in rats correlated well with human HPAH and IPAH lungs, respectively. A SU5416-CH (SuHx) PH model is well connected to the decompensated RVs of human PAH. Sex dimorphisms have been observed in PAH derived PAECs and PASMCs, independent of gonadal hormones. We conducted, for the first time, a meta-cohort and cross-species comparative study and identified optimal in vivo and in vitro PH model systems that recapitulate certain aspects of the human PH, which could provide novel insights into new therapeutic avenues in PH.
Category
Animal Models of Pulmonary Vascular Disease and Therapy
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Review Articles Concerning Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
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