The Transcriptome Expression Profiling Analysis Of Heart Failure With Atrial Fibrillation

Objective:Atrial fibrillation(AF)and heart failure(HF)are mutually causal and have complex pathogenesis,but the molecular mechanisms common to both are unclear.We focused on the identification of differentially expressed circular RNA(circRNA),long noncoding RNA(lncRNA)and messenger RNA(m RNA)in peripheral blood mononuclear cells(PBMCs)of patients with HF complicated with AF to investigate the role of ce RNA regulatory network in initiation and progression of disease.Methods:PBMCs were obtained from 4 patients who had heart failure with atrial fibrillation(HF/AF group)and 4 matched healthy subjects.RNA sequencing was performed to get circRNAs and m RNAs.mi RNAs were obtained through mi Randa and HMDD databases.Part1:R software was employed for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses.The PPI network was completed using STRING.Immune infiltration analysis was performed using cibersort method.The ce RNA network of circRNA/mi RNA/m RNA was constructed by Cytoscape.Part2:Firstly,GSEA was conducted to find the HF with AF-related pathways.Then,differentially expressed lncRNAs were obtained from R software.Ce RNA network was constructed through Cytoscape.On the one hand,gene sets of ferroptosis-related genes from Ferrdb and of the key pathways were used for screening the ce RNA network.On the other hand,we performed the coexpression analysis between lncRNAs and m RNAs to screen the network.Additionally,the spearman correlation analysis was conducted to discover the relationship between RNAs and immune cells in the disease.Finally,the biomarkers and RNAs closely related to the initiation and progression of heart failure with atrial fibrillation were screened by lasso regression analysis,and the final ce RNA regulatory axis was obtained.Results:Part1:Differential expression analysis showed that circRNAs(137 upregulated and31 downregulated)and m RNAs(534 upregulated and 225 downregulated)were considered as significantly different between HF/AF group and control group.Immune infiltration analysis demonstrated that macrophages were obviously upregulated and mast cells were significantly downregulated in PBMCs of the HF/AF group.GO and KEGG analyses showed that HF with AF-related m RNAs were abundant in the pathway of programmed cell death(PCD)and myocardial remodeling.We selected 5circRNA/mi RNA/m RNA axes from the intersections of PCD-related genes and ce RNA networks and sorted them according to the significance of the differences.It is suggested that PCD can promote the progression of HF with AF through PCD-related pathway.Part2: A total of 341 differential lncRNAs(121 up-regulated and 220down-regulated)were obtained by differential analysis.The PI3K-Akt signaling pathway and the biological process that regulate cellular responses to growth factor stimulation were considered as the key pathways in heart failure with atrial fibrillation.After screening,a total of 4 lncRNA/mi RNA/m RNA regulatory axes and 5 biomarkers were obtained.Conclusion:We suggested that imbalance of immune cell composition in PBMCs may play an initial role in the progression of HF with AF.There is differential expression of circRNA,lncRNA and m RNA in PBMCs in patients of heart failure with atrial fibrillation.Ce RNA regulatory networks associated with signaling pathways such as PCD and PI3K-Akt may be potential therapeutic targets for the occurrence and progression of heart failure with atrial fibrillation.CircRNA,lncRNA,and m RNA can be used as new diagnostic markers.