DOI: 10.1002/ame2.12486
Metabolic alterations in human pulmonary artery smooth muscle cells treated with PDGF-BB
Meng-Jie Zhang1
Jie-Jian Kou2
Hong-Da Zhang3
Xin-Mei Xie1
Yun-Feng Zhou1
Ping Yuan4
Xiao-Bin Pang1
Lu-Ling Zhao1
Jing Qiu5
Yang-Yang He1
1.School of Pharmacy,Henan University,Kaifeng,China2.Department of Pharmacy,Huaihe Hospital of Henan University,Kaifeng,China3.Department of Cardiology,State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China4.Department of Cardiopulmonary Circulation,Shanghai Pulmonary Hospital,Tongji University School of Medicine,Shanghai,China5.Department of Cardiology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,China
摘要：Background:Metabolic abnormalities are considered to play a key regulatory role in vascular remodeling of pulmonary arterial hypertension.However,to date,there is a paucity of research documenting the changes in metabolome profiles within the su-pernatants of pulmonary artery smooth muscle cells(PASMC)during their transition from a contractile to a synthetic phenotype.
Methods:CCK-8 and Edu staining assays were used to evaluate the cell viability and proliferation of human PASMCs.IncuCyte ZOOM imaging system was used to continuously and automatically detect the migration of the PASMCs.A targeted me-tabolomics profiling was performed to quantitatively analyze 121 metabolites in the supernatant.Orthogonal partial least squares discriminant analysis was used to dis-criminate between PDGF-BB-induced PASMCs and controls.Metabolite set enrich-ment analysis was adapted to exploit the most disturbed metabolic pathways.
Results:Human PASMCs exhibited a transformation from contractile phenotype to synthetic phenotype after PDGF-BB induction,along with a significant increase in cell viability,proliferation,and migration.Metabolites in the supernatants of PASMCs treated with or without PDGF-BB were well profiled.Eleven metabolites were found to be significantly upregulated,whereas seven metabolites were downregulated in the supernatants of PASMCs induced by PDGF-BB compared to the vehicle-treated cells.Fourteen pathways were involved,and pyruvate metabolism pathway was ranked first with the highest enrichment impact followed by glycolysis/gluconeogen-esis and pyrimidine metabolism.
Conclusions:Significant and extensive metabolic abnormalities occurred during the phenotypic transformation of PASMCs.Disturbance of pyruvate metabolism pathway might contribute to pulmonary vascular remodeling.
机标关键词：metabolicpdgf-bbhumancellswithalterationsarterymuscle
论文发表日期：2025-07-30
在线出版日期：2025-09-28（本平台首次上网日期，不代表文献的发表时间）
页数：9( 1268-1276 )
英文信息