The Four Key Genes Participated in and Maintained Atrial Fibrillation Process via Reprogramming Lipid Metabolism in AF Patients

Abstract

Atrial fibrillation (AF) is always in high incidence in the population, which can lead to serious complications. The structural and electrical remodeling of atrial muscle induced by inflammatory reaction or oxidative stress was considered as the major mechanism of AF. The treatment effect is not ideal based on current mechanisms. Recent studies demonstrated that lipid metabolism disorder of atrial muscle played an important role in the occurrence of AF. What key genes are involved is unclear. The purpose of the present study was to explore the lipid metabolism mechanism of AF. With the GEO database and the genomics of AF patients, metabolic related pathways and the key genes were analyzed. At the same time, the rat model of cecal ligation and puncture (CLP) was used to confirm the results. GSE 31821 and GSE 41177 were used as data sources, and the merged differentially expressed genes (DEGs) analysis showed that a total of 272 DEGs were found. GO annotation, KEGG, and gene set enrichment analysis (GSEA) showed that the fatty acid metabolism and the lipid biosynthetic process were involved in AF. Cholesterol biosynthesis, arachidonic acid metabolism, and the lipid droplet pathway were obviously increased in AF. Further analysis showed that four key genes, including ITGB1, HSP90AA1, CCND1, and HSPA8 participated in pathogenesis of AF regulating lipid biosynthesis. In CLP rats, metabolic profiling in the heart showed that the pyrimidine metabolism, the biosynthesis of unsaturated fatty acid metabolism, arginine and proline metabolism, and the fatty acid biosynthesis were involved. The four key genes were confirmed increased in the heart of CLP rats (p < 0.05 or 0.01). The results suggest that the lipid metabolism disorder participates in the occurrence of AF. ITGB1, HSP90AA1, CCND1, and HSPA8 are the key genes involved in the regulation of lipid biosynthesis.

Association between triglyceride-glucose index and atrial fibrillation: A retrospective observational study

“…In our study, we showed the TC and LDL-C levels in AF group are significantly lower than the control. The lipid metabolism disorder might play a key role in the pathogenesis of AF ( 37 ). However, previous studies have identified higher levels of TC and LDL-C are associated with a lower incidence of AF ( 38 , 39 ).…”

Integrative single-cell RNA sequencing and metabolomics decipher the imbalanced lipid-metabolism in maladaptive immune responses during sepsis

“…The numerical simulation method fills in half of the minimum value. The resulting three-dimensional data, which included peak number, sample name, and normalized peak area, were input into the SIMCA14+ metaboanalyst tool package (Umetrics, Umea, Sweden) for PCA analysis ( 26 ). The significantly different expressions of metabolites and metabolic pathways were analyzed by heatmap and bubble plot.…”

The Impact of Sleep Disturbance on Gut Microbiota, Atrial Substrate, and Atrial Fibrillation Inducibility in Mice: A Multi-Omics Analysis

“…Meanwhile, the direct interaction between disordered GM and AF has been confirmed [17]. The dysbiosis of GM composition and function is closely linked to AF onset, duration, type, and recurrence [14][15][16]35], especially the imbalance of GM-derived metabolites, including lipopolysaccharide (LPS), trimethylamine N-oxide (TMAO), SCFAs, and bile acids (BAs), which are involved in inflammation, fibrosis and disordered lipid metabolism, and may lead to AF progression [11,17,[36][37][38][39]. A recent large-scale 10-year follow-up cohort study [7] suggested that longer lifetime durations and 3-8 nights/month frequency of night shift work exposure are associated with higher AF risk.…”