The Study Of LncRNAs And MRNAs Expression Of Auricula Dextra In Patients With Pulmonary Hypertension Secondary To Ventricular Septal Defect

Objective:Comparing study of LncRNAs and mRNAs expression of auricula dextra in Patients with pulmonary hypertension secondary to ventricular septal defect to provide data base for further research of LncRNA related pulmonary hypertension.Methods:Total RNA was extracted from 4 samples of moderate-severe PAH secondary to VSD in experiment group and 4 samples with simply VSD,these samples were acquired from auricula dextra tissue during surgical operation before cardio-pulmonary bypass.After quality inspection,the qualified RNA was used to hybrid synthesize cDNA.Scanning the hybridization chip to get the preliminary results,which were converted and analyzed to obtain the data of mRNA and LncRNA.Fold Change>2,P<0.05 as the difference of gene expression inclusion criteria to get LncRNAs and mRNAs expression profile.and through the scatter Plot and theVolcano Plot to visualize the marked differences of LncRNAs and mRNAs,and then the data were analysed by cluster analysis,and the relevant Biological information of these results were obtained by Gene ontology analysis and KEGG Pathway analysis.Results:Compared with the control group,in experimental group,813 LncRNAs up-regulated（26 LncRNAs,FoldChange>10 anduc004aef.3 was the most up-regulated LncRNA with FoldChange=106）,541 LncRNAs down-regulated（4 LncRNAs,FoldChange>10 and ENST00000580684 was the most down-regulated LncRNA with FoldChange=16）.Meanwhile 527 mRNAs up-regulated（13 mRNAs,FoldChange>10 and NM₀04887 was the most up-regulated mRNA with FoldChange=24）and 268 mRNAs down-regulated（7 mRNAs,FoldChange>10 and NM 005484 was the most down-regulated mRNA with FoldChange=31）.These results suggested that the differential expression LncRNAs might be involved in regulating the progress of PAH by regulating mRNAs expression widely.But the research on the regulatory mechanism of LncRNAs on pulmonary arterial pressure is very little,due to lack of LncRNAs data base query.of pulmonary hypertension,the relationship between LncRNAs and mRNAs is still unclear.The GO analysis results on different expression mRNAs suggested which were relevant with the inflammatory response,extra-cellular matrix,muscle cell differentiation,sarcomere,muscle cell differentiation,protein domain specific binding,endo-peptidase inhibitor,calmodulin-dependent protein kinase activity,voltage-gated ion channel activity,cation channel activity.At present,a large number of research literatures show these pathophysiological changes existed widely in pulmonary artery hypertension process.KEGG Pathway analysis indicated that the up-regulated mRNAs enriched in 14 pathways and the top 2 enriched pathways were Peroxisome Proliferator-Activated Receptor signaling pathway and Complement and coagulation cascades.Moreover,the down-regulated mRNAs enriched in 15 pathways and the top 2 enriched pathways were Antigen processing and presentation and Graft-versus-host sease.Allthe 29 pathways might be associated with PAH.5 pathways of them were consistent with what has been reported in some literatures,including the first,the second,the fourth,the eleventh highest enrichment pathways in up-regulated mRNAs and the third highest enrichment pathway in down-regulated mRNAs.There was no literature reported the other 24 pathways were associated with PAH.These pathways discovered in our experiment,especially the down-regulated mRNAs enriched Antigen processing and presentation pathway and Graft-versus-host disease pathway and the third highest enrichment up-regulated mRNAs pathway measles,which maybe research direction in the mechanism of pulmonary artery hypertension.Conclusion:Due to the right atrial appendage was easily acquired,and not violate the medical ethics,which was good source to research the mechanism of the pulmonary artery hypertension secondary to ventricular septal defect with significantly changed LncRNA.26 significantly up-regulated（FoldChange>10）and 4 down-regulated（F oldChange>10）LncRNAs and 13 significantly up-regulated（FoldChange>10）and 7 down-regulated（FoldChange>10）mRNAs were screened by LncRNA microarrayGene chip technology in human right atrial appendage with pulmonary artery hypertension secondary to ventricular septal defect.These LncRNAs and mRNAs may become new biological marker protein for further study of gene diagnosis of pulmonary arterial hypertension.The GO analysis showed that the pathophysiological changes brought by differential expression mRNAs in right atrial appendage were highly correlated with pulmonary arterial hypertension.KEGG Pathway analysis indicated that 29 pathways might be associated with PAH.5 pathways of them were consistent with what has been reported in some literatures.There was no literature reported the other 24 pathways were associated with PAH.Within these pathways,thedown-regulated enriched mRNAs pathway Antigen processing and presentation pathway,Graft-versus-host disease pathway and the up-regulated enriched mRNAs measles pathway are worthy of further study.