Siqi She, Debao Li, Qi Sun, Lincai Ye
Shanghai Children’s Medical Center and Shanghai Jiao Tong University School of Medicine. Children’s Hospital of Fudan University and National Children’s Medical Center.
China
Children
Children 2026; 13:
DOI: 10.3390/children13050677
Abstract
Pulmonary vein stenosis (PVS) is a rare and devastating condition affecting infants and children, characterized by progressive intimal hyperplasia, myofibroblast proliferation, and extracellular matrix deposition, leading to pulmonary hypertension and right heart failure. Despite multimodal interventions including surgery and catheter-based approaches, long-term outcomes remain poor due to high rates of restenosis and disease progression. The development of representative animal models has been instrumental in unraveling the complex pathophysiology of PVS and identifying potential therapeutic targets. This review comprehensively examines the evolution of PVS animal models-from large animals to recently established rodent models-and synthesizes insights gained regarding key pathogenic pathways and their therapeutic implications in guiding associated clinical trials in pediatric patients. We discuss evidence supporting mammalian target of rapamycin (mTOR) inhibition, TGF-β, platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) targeting, and emerging strategies including fibroblast activation protein (FAP) inhibition and YAP/β-catenin pathway modulation. The recent development of neonatal rat PVS models has accelerated translational research by enabling cost-effective, high-throughput evaluation of candidate therapies. We propose a mechanistic framework integrating these pathways and discuss future directions for precision medicine approaches in PVS.
Category
Stenosis or Obstruction of Normal Pulmonary Venous Connections
Stenosis or Obstruction of Pulmonary Veins Following Surgical Repair of Anomalous Pulmonary Venous Connections
Medical Therapy to Prevent or Reverse the Onset of Disease. Efficacy or Lack of Efficacy
Medical Therapy to Prevent Progression of Disease. Efficacy or Lack of Efficacy
Medical Therapy to Prevent Recurrence of Disease after an Intervention. Efficacy or Lack of Efficacy
Year of Publication: 2026
Age Focus: Pediatric
Article Type: Review
Article Access: Free PDF File or Full Text Article Available Through PubMed or DOI: Yes