Fang Yijin, Wu Yue, Liu Liangming, Wang Huadong
Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, Guangzhou, China.
State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department of Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.
Front Genet. 2022 May 20;13:821754. doi: 10.3389/fgene.2022.821754. eCollection 2022.
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 ( < 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.
心房颤动（AF）在人群中发病率一直很高，可导致严重并发症。炎症反应或氧化应激诱导的心房肌结构和电重构被认为是AF的主要机制。基于目前的机制，治疗效果并不理想。最近的研究表明，心房肌脂质代谢紊乱在AF的发生中起重要作用。涉及哪些关键基因尚不清楚。本研究的目的是探讨AF的脂质代谢机制。利用GEO数据库和AF患者的基因组学，分析了代谢相关途径和关键基因。同时，采用盲肠结扎和穿刺（CLP）大鼠模型来证实结果。以GSE 31821和GSE 41177作为数据源，合并差异表达基因（DEG）分析显示共发现272个DEG。基因本体（GO）注释、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）表明，脂肪酸代谢和脂质生物合成过程与AF有关。AF中胆固醇生物合成、花生四烯酸代谢和脂滴途径明显增加。进一步分析表明，包括整合素β1（ITGB1）、热休克蛋白90α家族成员1（HSP90AA1）、细胞周期蛋白D1（CCND1）和热休克蛋白70家族成员8（HSPA8）在内的四个关键基因参与了AF调节脂质生物合成的发病机制。在CLP大鼠中，心脏代谢谱分析表明嘧啶代谢、不饱和脂肪酸代谢生物合成、精氨酸和脯氨酸代谢以及脂肪酸生物合成均参与其中。证实这四个关键基因在CLP大鼠心脏中增加（<0.05或0.01）。结果表明脂质代谢紊乱参与了AF的发生。ITGB1、HSP90AA1、CCND1和HSPA8是参与脂质生物合成调节的关键基因。
