Kamihara Takahiro, Hirashiki Akihiro, Kokubo Manabu, Shimizu Atsuya
Department of Cardiology, National Center for Geriatrics and Gerontology Obu Japan.
Circ Rep. 2023 Mar 24;5(4):114-122. doi: 10.1253/circrep.CR-22-0130. eCollection 2023 Apr 10.
Autophagy may contribute to the maintenance of atrial fibrillation (AF), but no previous study has concurrently surveyed all 3 phases of autophagy, namely autophagosome formation, lysosome formation, and autophagosome-lysosome fusion. Here we aimed to identify disorders involving various phases of autophagy during AF. We used bioinformatic techniques to analyze publicly available DNA microarray datasets from the left atrium (LA) and right atrium (RA) of 7 patients with AF and 6 patients with normal sinus rhythm who underwent valvular surgeries. We compared gene expression levels in the LA (AF-LA) and RA of patients with AF with those in the LA and RA of patients with normal sinus rhythm. Several differentially expressed genes in the AF-LA sample were significantly associated with the Gene Ontogeny term 'Autophagy', indicating that the expression of autophagic genes was specifically altered in this dataset. In particular, the expression of genes known or suspected to be involved in autophagosome formation (autophagy related 5 [], autophagy related 10 [], autophagy related 12 [], and light chain 3B []), lysosome formation (lysosomal associated membrane protein 1 [] and lysosomal associated membrane protein 2 []), and autophagosome-lysosome fusion (synaptosome associated protein 29 [], SNAP associated protein [], and syntaxin 17 []) was significantly upregulated in the LA-AF dataset. Autophagy is activated excessively in, and may perpetuate, AF.
自噬可能有助于心房颤动(AF)的维持,但此前尚无研究同时调查自噬的所有三个阶段,即自噬体形成、溶酶体形成和自噬体-溶酶体融合。在这里,我们旨在确定AF期间涉及自噬各个阶段的紊乱情况。我们使用生物信息学技术分析了7例AF患者和6例接受瓣膜手术的正常窦性心律患者的左心房(LA)和右心房(RA)的公开可用DNA微阵列数据集。我们比较了AF患者的LA(AF-LA)和RA与正常窦性心律患者的LA和RA中的基因表达水平。AF-LA样本中的几个差异表达基因与基因本体术语“自噬”显著相关,表明该数据集中自噬基因的表达发生了特异性改变。特别是,已知或怀疑参与自噬体形成(自噬相关5、自噬相关10、自噬相关12和轻链3B)、溶酶体形成(溶酶体相关膜蛋白1和溶酶体相关膜蛋白2)以及自噬体-溶酶体融合(突触体相关蛋白29、SNAP相关蛋白和 syntaxin 17)的基因在LA-AF数据集中的表达显著上调。自噬在AF中被过度激活,并且可能使AF持续存在。