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

Abstract

ObjectiveSympathetic 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 resultsM0- 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.ConclusionsWe 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.

Noncoding RNAs as Key Regulators for Cardiac Development and Cardiovascular Diseases

“…In addition, RNA pull-down assays demonstrated that LOC10 might interact with growth-associated protein 43 (GAP43). The results further supported the reduction in GAP43 expression and in VA incidence after LOC10 knockdown in rat hearts following adeno-associated virus (AAV) injection [90]. This study demonstrated the role of the LOC10/GAP43 axis in the regulation of VA.…”

“…NcRNAs are important regulators of inflammation and sympathetic remodeling following MI. Li et al identified and characterized lncR-NAs that are potentially implicated in VA following MI [90]. In their study, differentially expressed lncRNAs were identified by RNA-seq on nonactivated M0-and proinflammatory M1-type macrophages.…”