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Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet
Published on: November 4, 2015
Therapeutic Targets for Pediatric Pulmonary Vein Stenosis: Insights from Animal Models
1Shanghai Institute for Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Insights
Pulmonary vein stenosis (PVS) in children is a severe condition with poor outcomes. New animal models, especially in rodents, are accelerating research into targeted therapies for this rare disease.
Area of Science:
- Pediatric Cardiology
- Vascular Biology
- Translational Medicine
Background:
- Pulmonary vein stenosis (PVS) is a rare pediatric condition causing pulmonary hypertension and heart failure.
- Current treatments offer limited long-term success due to restenosis and disease progression.
Purpose of the Study:
- To review the evolution and utility of animal models for studying PVS pathophysiology.
- To synthesize findings on key pathogenic pathways and therapeutic targets for PVS.
- To guide future clinical trials and precision medicine in pediatric PVS.
Main Methods:
- Comprehensive review of existing literature on PVS animal models, from large animals to rodents.
- Analysis of pathogenic mechanisms including intimal hyperplasia and myofibroblast proliferation.
- Evaluation of therapeutic strategies targeting mTOR, TGF-β, PDGF, VEGF, FAP, and YAP/β-catenin.
Main Results:
- Rodent models, particularly neonatal rat models, offer cost-effective, high-throughput evaluation of therapies.
- Key pathways identified include mTOR, TGF-β, PDGF, VEGF, FAP, and YAP/β-catenin.
- Animal models have been crucial for understanding PVS pathogenesis and identifying therapeutic targets.
Conclusions:
- Advancements in PVS animal models are crucial for accelerating research and developing effective treatments.
- Targeting specific molecular pathways shows promise for improving outcomes in pediatric PVS.
- Future research should focus on integrating mechanistic insights for precision medicine approaches in PVS.
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.
