DOI: 10.1002/ame2.12191
Implication of proliferation gene biomarkers in pulmonary hypertension
Yi Yan1
Rong Jiang2
Ping Yuan2
Li Wen3
Xiao-Bin Pang4
Zhi-Cheng Jing5
Yang-Yang He4
Zhi-Yan Han6
1.Institute for Cardiovascular Prevention (IPEK) , Ludwig- Maximilians- University Munich , Munich , Germany;DZHK (German Centre for Cardiovascular Research) , partner site Munich Heart Alliance , Munich , Germany2.Department of Cardio- Pulmonary Circulation , Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai , China3.Department of Cardiology , The First Affiliated Hospital, Chongqing Medical University , Chongqing , China4.School of Pharmacy , Henan University , Henan , China5.State Key Laboratory of Complex, Severe, and Rare Diseases, and Department of Cardiology , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China6.State Key Laboratory of Cardiovascular Disease and FuWai Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
摘要：Objective/Background : Proliferation is a widely recognized trigger for pulmonary hypertension (PH), a life- threatening, progressive disorder of pulmonary blood ves-sels. This study was aimed to identify some proliferation associated genes/targets for better comprehension of PH pathogenesis.Methods : Human pulmonary arterial smooth muscle cells (hPASMCs) were cultured in the presence or absence of human recombinant platelet derived growth factor (rhPDGF)- BB. Cells were collected for metabolomics or transcriptomics study. Gene profiling of lungs of PH rats after hypoxia exposure or of PH patients were retrieved from GEO database. Results : 90 metabolites (VIP score >1, fold change >2 or <0.5 and p < .05) and 2701 unique metabolism associated genes (MAGs) were identified in rhPDGF- BB treated hPASMCs compared to control cells. In addition, 1151 differentially expressed genes (313 upregulated and 838 downregulated) were identified in rhPDGF- BB treated hPASMCs compared to control cells (fold change >2 or <0.5 and p < .05). 152 dif-ferentially expressed MAGs were then determined, out of which 9 hub genes (IL6, CXCL8, CCL2, CXCR4, CCND1, PLAUR, PLAU, HBEGF and F3) were defined as core proliferation associated hub genes in protein proten interaction analysis. In addition, the hub gene- based LASSO model can predict the occurrence of PH (AUC = 0.88).The expression of CXCR4, as one of the hub genes, was positively correlated to im-mune cell infiltrates. Conclusion : Our findings revealed some key proliferation associated genes in PH, which provide the crucial information concerning complex metabolic reprogramming and inflammatory modulation in response to proliferation signals and might offer therapeutic gains for PH.
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论文发表日期：2021-12-25
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：12( 369-380 )
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