Adipocyte-related genes analysis contributes to the prognosis of atrial fibrillation

Abstract

BackgroundPatients with mild left atrial appendage fibrosis have a significantly lower rate of atrial fibrillation (AF) recurrence after 5 years compared to those with moderate or severe fibrosis, which presented a significantly increased positive area of cellular senescence. MethodsGSE135445, a RNA-sequencing dataset between epicardial adipose tissue (EAT) from patients with persistent non-valvular AF and sinus rhythm (SR), was downloaded and analyzed and hub genes were obtained. To obtain the abundance of immune cells, the CIBERSORT algorithm with 100 permutations was applied. The senescent hub genes were obtained and validated using human blood samples. ResultsA total of 164 up-regulated and 317 down-regulated DEGs was obtained between EAT from subjects with AF and SR. Using immune infiltration analysis in whole PAT related DEGs, the abundance of M0 macrophages was significantly different between PAT and SAT and 22 M0 macrophages-related DEGs were also obtained, such as MMP7, APOE, CCND1, MMP12 and APOC1. Venn diagram was utilized to obtain the same transcripts between senescence datasets and DEGs and PPI network was used to 94 overlapping genes. The top15-degree senescence adipicytes hub genes were explored. To investigate senescence-related hub genes effects on AF progression, we collected the blood samples of patients with paroxysmal atrial fibrillation and persistent atrial fibrillation. There were no significant differences at baseline characteristics and laboratory examinations at 1d after admission except heart failure history and function examinations, for instance, ALT, LDL, LVEF and LA diameters. Using univariate analysis and multivariate analysis, heart failure history, ALT and LA diameters can be prognostic factors for AF progression. BMP7, COL4A3, COL4A4, CHRD, IRX1, SPON1, ALPL, TCF19 and SIX2 were validated to be highly expressed in persistent atrial fibrillation compared to paroxysmal atrial fibrillation. ConclusionBased on our current study, BMP7, COL4A3, COL4A4, CHRD, IRX1, SPON1, ALPL, TCF19 and SIX2 were validated to be highly expressed in persistent atrial fibrillation compared to paroxysmal atrial fibrillation, which may be potential therapeutic targets to treat AF progression and improve patients prognosis.