Transcriptome analysis of canine cardiac fat pads: involvement of two novel long non-coding RNAs in atrial fibrillation neural remodeling.

Abstract

Intrinsic cardiac autonomic neural remodeling (ANR) has been reported to be involved in the initiation and maintenance of atrial fibrillation (AF). Long non-coding RNAs (lncRNAs) are important orchestrators of gene regulatory networks. However, little is known about the relationships between lncRNAs and cardiac ANR in AF. In this study, second-generation RNA sequencing was performed to examine the transcriptomes of lncRNAs in AF and non-AF canine cardiac fat pads. A total of 61,616 putative lncRNAs were yielded, in which 166 were downregulated and 410 were upregulated with more than twofold change. Bioinformatics analysis showed that the aberrantly expressed genes were associated with neural development, migration and neurodegenerative disorders. On the basis of a series of filtering pipelines, two new lncRNAs, namely, TCONS_00032546 and TCONS_00026102, were selected. Silencing of TCONS_00032546 or TCONS_00026102 with lentiviruses in vivo could significantly shorten or prolong the atrial effective refractory period thereby increasing or preventing AF inducibility by promoting or inhibiting the neurogenesis. Besides, the expression of CCND1-FGF19-FGF4-FGF3 gene cluster and SLC25A4, the nearby genes of TCONS_00032546 and TCONS_00026102, were negatively correlated with that of lncRNAs. Furthermore, combining bioinformatics analysis with literature review, TCONS_00032546 and TCONS_00026102 may induce effects by increasing the CCND1-FGF19-FGF3-FGF4 gene cluster and SLC25A4 via complex mechanisms during neural remodeling. Taken together, dysregulated lncRNAs may play regulatory roles in AF neural remodeling, which may further provide potential therapeutic targets for prophylaxis and treatment of AF.