Bioinformatics Analysis Of Differential Gene Expression Profiles For Persistent Atrial Fibrillation And Heart Failure With Reduced Ejection Fraction

Background and aim:Atrial fibrillation(AF)and Heart failure(HF)are two common diseases,which are the two "fortresses" in the field of cardiovascular diseases which have not yet been overcome in the 21 st century.As risk factors of AF and HF becomes more common and global aging becomes more severe,the prevalence of these two diseases has continued to rise,which led to lower patients' quality of life,reduced exercise tolerance,and increased hospitalization or all-cause mortality.The specific molecular mechanisms of occurrence and development of the diseases were not clear yet.Previous studies showed that the underlying mechanisms were a complex dynamic process involving multiple cells and pathways.However,patients' myocardial tissues were difficult to obtain so there were fewer published papers and fewer consistent results.The gene expressing regulations and mechanisms of AF and HF are still difficult for current research.In this study,we analyzed big data about the differential gene expression profiles of myocardial tissues in patients with persistent AF and heart failure with reduced ejection fraction(HFrEF)in order to explain the pathogenesis of AF and HFrEF,explore the internal relationship between AF and HFrEF in depth,provide theoretical reference for early prevention and diagnosis,and screen therapeutic targets.Methods:Using the gene expression database GEO of NCBI,data sets related to persistent AF and HFrEF were obtained.After the preprocessing of the original data,t SNE analysis,hierarchical clustering analysis and gene enrichment analysis were carried out,and through differential genes screening,DEGs of persistent AF and HFrEF were determined respectively.Next,GO and KEGG databases were used to analyze the biological functions and pathways of DEGs and using the protein-protein interaction database STRING to assess the biological correlation between differential genes.Results:1.There were 539 AF-related DEGs,of which 387 genes were up-regulated and 152 genes were down-regulated.These genes were mainly involved in myocardial tissue development,fibroblast proliferation regulation,MAP kinase activity regulation,pyruvate metabolism,extracellular matrix regulation,etc.KEGG analysis found that the up-regulated gene set was mainly enriched in m TOR signaling pathway,Toll-like receptor signaling pathway,extracellular matrix receptor interaction,adhesion spot,chemokine signaling pathway,cell cycle,etc.Down-regulated gene set was mainly enriched in Erb B signaling pathway,Hedgehog signaling pathway,Wnt signaling pathway,calcium signaling pathway,etc.PPI network analysis showed that CDH2,PDGFA,ITGA6,COL1A1,EGFR,FGFR2,ERBB3 and WNT5 A may play important roles in the mechanisms of proteins expression regulation in AF.2.There were 49 HFrEF-related DEGs,of which 30 genes were up-regulated and 19 genes were down-regulated.These genes were closely related to the occurrence and development of HFrEF through participation in tissue fibrosis,cell matrix adhesion regulation,metabolic regulation,inflammatory response,etc.KEGG analysis found that the up-regulated gene set was mainly enriched in WNT signaling pathway,calcium signaling pathway,oxidative phosphorylation,antigen processing and presentation,cell adhesion molecules,extracellular matrix receptor interaction,etc.Down-regulated gene set was mainly enriched in Erb B signaling Pathway,vascular endothelial growth factor signaling pathway,MAPK signaling pathway,arachidonic acid metabolism,etc.PPI network analysis showed that PTN,POSTN,LUM,NPPA,CCL2 and SERPINE1 may play important roles in the mechanisms of proteins expression regulation in HFrEF.3.Persistent AF and HFrEF had three common DEGs: LTBP2,HAPLN1 and CRYM.KEGG analysis found that the simultaneously up-regulated gene set in myocardial tissue of HFrEF and AF was mainly enriched in extracellular matrix receptor interactions,viral myocarditis and antigen processing presentation.In addition,the simultaneously down-regulated gene set in myocardial tissue of HFrEF and AF was mainly enriched in Erb B signaling pathway.Conclusion: Bioinformatics analysis of chip data revealed that up-regulation of CDH2,PDGFA,ITGA6,COL1A1,YWHAZ,CXCR4,and down-regulation of EGFR,FGFR2,ERBB3,WNT5 A may play a crucial role in the development of persistent AF;Up-regulation of PTN,POSTN,LUM,SFRP1,FMOD,NPPA,and down-regulation of CCL2,CD163,SERPINE1 and S100A8 genes may play a crucial role in the development of HFrEF;The up-regulation of LTBP2,HAPLN1,CRYM and the downregulation of Erb B signaling pathway may also correspond to the coexistence of the persistent AF and HFrEF.