Li Pingjiang, Wang Kang, Yin Jie, Qi Lei, Hu Hesheng, Yang Peijin, Shi Yugen, Li Yan, Feng Meng, Lyu Hangji, Ge Weili, Li Xiaolu, Yan Suhua
Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Cardiac Electrophysiology and Arrhythmia, Jinan, China.
Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Front Cardiovasc Med. 2023 Jan 6;9:1019435. doi: 10.3389/fcvm.2022.1019435. eCollection 2022.
Sympathetic remodeling after myocardial infarction (MI) is the primary cause of ventricular arrhythmias (VAs), leading to sudden cardiac death (SCD). M1-type macrophages are closely associated with inflammation and sympathetic remodeling after MI. Long noncoding RNAs (lncRNAs) are critical for the regulation of cardiovascular disease development. Therefore, this study aimed to identify the lncRNAs involved in MI and reveal a possible regulatory mechanism.
M0- and M1-type macrophages were selected for sequencing and screened for differentially expressed lncRNAs. The data revealed that lncRNA LOC100911717 was upregulated in M1-type macrophages but not in M0-type macrophages. In addition, the lncRNA LOC100911717 was upregulated in heart tissues after MI. Furthermore, an RNA pull-down assay revealed that lncRNA LOC100911717 could interact with growth-associated protein 43 (GAP43). Essentially, immunofluorescence assays and programmed electrical stimulation demonstrated that GAP43 expression was suppressed and VA incidence was reduced after lncRNA LOC100911717 knockdown in rat hearts using an adeno-associated virus.
We observed a novel relationship between lncRNA LOC100911717 and GAP43. After MI, lncRNA LOC100911717 was upregulated and GAP43 expression was enhanced, thus increasing the extent of sympathetic remodeling and the frequency of VA events. Consequently, silencing lncRNA LOC100911717 could reduce sympathetic remodeling and VAs.
心肌梗死（MI）后的交感神经重塑是室性心律失常（VA）的主要原因，可导致心源性猝死（SCD）。M1型巨噬细胞与MI后的炎症和交感神经重塑密切相关。长链非编码RNA（lncRNA）对心血管疾病发展的调控至关重要。因此，本研究旨在鉴定参与MI的lncRNA，并揭示一种可能的调控机制。
选择M0型和M1型巨噬细胞进行测序，并筛选差异表达的lncRNA。数据显示lncRNA LOC100911717在M1型巨噬细胞中上调，但在M0型巨噬细胞中未上调。此外，lncRNA LOC100911717在MI后的心脏组织中上调。此外，RNA下拉试验表明lncRNA LOC100911717可与生长相关蛋白43（GAP43）相互作用。本质上，免疫荧光试验和程控电刺激表明，使用腺相关病毒在大鼠心脏中敲低lncRNA LOC100911717后，GAP43表达受到抑制，VA发生率降低。
我们观察到lncRNA LOC100911717与GAP43之间存在一种新的关系。MI后，lncRNA LOC100911717上调，GAP43表达增强，从而增加了交感神经重塑的程度和VA事件的频率。因此，沉默lncRNA LOC100911717可减少交感神经重塑和VA。
