Yanfang Zong, Wei Liu, Jiahe Tian, Cuilan Hou, Tingting Xiao, Sirui Song, Xunwei Jiang
Shanghai Children’s Hospital School of Medicine and Shanghai Jiao Tong University.
China
Translational Pediatrics
Transl Pediatr 2025; 14: 2572-2585
DOI: 10.21037/tp-2025-370
Abstract
Background: Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease causing right heart failure. Idiopathic PAH (IPAH), a type of PAH with unknown causes, has a particularly poor prognosis. Current targeted therapies are insufficient, highlighting the need for new therapeutic targets and biomarkers. This study aims to identify potential metabolic biomarkers and dysregulated pathways for the diagnosis and treatment of IPAH through integrated metabolomic and transcriptomic analyses.
Methods: This study enrolled PAH patients [2023-2024] and collected pretreatment blood samples, using healthy children as controls. RNA sequencing analyzed gene expression in peripheral blood mononuclear cells (PBMCs), and liquid chromatography-mass spectrometry (LC-MS) detected blood metabolites. Metabolites were identified via multiple databases, and bioinformatics analyses [principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA)] explored PAH’s molecular mechanisms.
Results: In PAH patients, 1,629 differentially expressed genes (DEGs) were found, with 802 upregulated and 827 downregulated genes, enriched in cell cycle regulation, stress response, and mitochondrial dysfunction. Metabolomics showed 30 upregulated and 29 downregulated metabolites, mainly in amino acid and energy metabolism. Key genes like LDHB and IRS2, and metabolites such as glucose and L-glutamine, are closely linked to PAH’s pathology, especially in glycolysis pathways.
Conclusions: The study underscores the intimate connection between transcription factor (e.g., JUNB, ZNF281)-regulated gene expression (e.g., LDHB, IRS2) and metabolite (e.g., glucose, L-glutamine) alterations in PAH, revealing that key genes and metabolites closely tied to the disease’s pathology.
Category
Class I. Idiopathic Pulmonary Hypertension
Class I. Heritable Pulmonary Hypertension
Genetic Factors Associated with Pulmonary Vascular Disease
Potential Biomarkers Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes