Diversity among differentially expressed genes in atrial appendages of atrial fibrillation: The role and mechanism of SPP1 in atrial fibrosis.

BACKGROUND

Structural remodeling plays an important role in the occurrence and maintenance of atrial fibrillation (AF), but the mechanism is currently unclear. This study was designed to investigate the transcriptomic mechanism of structural remodeling of AF through bioinformatic analysis and in vivo and vitro experiments.

METHODS

Transcriptomic datasets were retrieved from the Gene Expression Omnibus (GEO) database, and bioinformatics analysis was performed to screen mRNAs associated with AF. Cell and animal models were constructed to verify the bioinformatic findings using RT-qPCR and western blot analysis. Then, SPP1 was screened as the target gene, and the mechanism by which it promotes fibrosis was further studied in human cardiac fibroblasts (HCFs) using western blot analysis.

RESULTS

After retrieval, the GSE14975, GSE31821, GSE79768, GSE115574 and GSE128188 datasets were used in this study. In total, 147 differentially expressed genes (DEGs) were identified in left atrial appendix tissue and 85 in right atrial appendix tissue. According to the enrichment analysis results, the calcium signaling pathway was found to play an important role in AF, in which EGFR, AGTR1, HTR2B, CD38 and BDKRB1 might be the key genes. Moreover, SPP1 was identified as a key driver through PPI analysis and experimentally proved to reduce the expression of p27 by regulating the PI3K/Akt signaling pathway, sequentially promoting HCF fibrosis.

CONCLUSION

Bioinformatics analysis showed that the calcium signaling pathway might play an important role in AF, while SPP1 could promote myocardial fibrosis through the PI3K/Akt/p27 signaling axis.