肺动脉高压相关线粒体自噬生物标志物及其作用的分析与验证OACSTPCD

Objective:To screen the differentially expressed genes of mitochondrial autophagy associated with pulmonary arterial hypertension(PAH)by bioinformatics,and to provide a new basis for further study of mito-chondrial autophagy.Methods:The PAH related dataset was downloaded from the Gene Expression Omnibus(GEO),and was divided into test and validation sets.Mitochondrial autophagy related genes were downloaded from the Molecular Signatures Database(MSigDB)and pathway unified database.The differentially expressed genes associated with mitochondrial autophagy in PAH were screened and analyzed for Gene Ontology(GO)an-notation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interac-tion,etc.The biomarkers were verified by validation set,and hub genes with significant differences and consis-tent differences were validated by receiver operating characteristic(ROC)curve.Peripheral blood of 32 children with congenital heart disease(CHD)-associated PAH(PAH-CHD)and CHD were collected for reverse transcrip-tion-quantitative polymerase chain reaction(RT-qPCR)expression verification of hub genes.Results:The data sets GSE113439,GSE15197,GSE117261 were collected as the test set,and GSE38267 as the verification set.A total of 11 differentially expressed genes of mitochondrial autophagy associated with PAH were obtained.These genes were mainly concentrated in mitophagy-animal,pathways of neurodegeneration-multiple diseases,autopha-gy-animal,Shigellosis,adherens junction,endocytosis,Parkinson's disease,etc.Among them,five hub genes(GABARAPL2,OPTN,RNF41,SRC,UBB)showed significant differences between PAH and normal groups in the combined data set and validation set,and the difference trend was consistent.The mRNA expression of GAB-ARAPL2,OPTN and UBB in the peripheral blood of PAH-CHD group was consistent with the predicted trend,while the mRNA expression of GABARAPL2 in the peripheral blood of PAH-CHD group was significantly in-creased(P<0.05).Conclusion:GABARAPL2 may play a regulatory role in mitochondrial autophagy associated with PAH.The specific mechanism still needs to be further verifiedin vivoandin vitro.