lncRNA LOC100911717-targeting GAP43-mediated sympathetic remodeling after myocardial infarction in rats.

1. Front Cardiovasc Med. 2023 Jan 6;9:1019435. doi: 10.3389/fcvm.2022.1019435. eCollection 2022.

lncRNA LOC100911717-targeting GAP43-mediated sympathetic remodeling after myocardial infarction in rats.

Li P(1)(2), Wang K(3), Yin J(1), Qi L(1)(2), Hu H(1), Yang P(1)(2), Shi Y(1), Li Y(4), Feng M(1)(2), Lyu H(1)(2), Ge W(5), Li X(1), Yan S(1).

Author information: (1)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. (2)Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. (3)Department of Cardiology, Cheeloo College of Medicine, Shandong Qianfoshan Hospital, Shandong University, Jinan, China. (4)Shandong Medicine and Health Key Laboratory of Cardiac Electrophysiology and Arrhythmia, Medical Research Center, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China. (5)Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Taizhou, Zhejiang, China.

OBJECTIVE: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Copyright © 2023 Li, Wang, Yin, Qi, Hu, Yang, Shi, Li, Feng, Lyu, Ge, Li and Yan.

DOI: 10.3389/fcvm.2022.1019435 PMCID: PMC9859628 PMID: 36684596

Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.