The integrative network of circRNA, miRNA and mRNA of epicardial adipose tissue in patients with atrial fibrillation.

introductionAtrial fibrillation (AF) is a highly prevalent cardiac arrhythmia that affects approximately 1-2% of the general population. The mechanism of AF pathogenesis remains unclear. Epicardial adipose tissue (EAT), a metabolically active visceral fat depot surrounding the heart, has been shown to be closely related to AF. EAT has a biological impact on neighboring myocardium by producing a myriad of bioactive molecules, including exosomes carrying circular RNAs (circRNAs). As a new category of noncoding RNAs, circRNAs can work as efficient sponges for specific microRNAs and efficiently regulate gene expression. MATERIAL AND

methodsTo investigate the regulatory mechanism of circRNAs of EAT in patients with AF, we collected EAT from AF (n=6) patients and non-AF (n=6) controls and profiled their circRNA expression with the RNA-sequencing method.

resultsRNA sequencing detected a total of 2159 circRNAs in EAT, among which 528 were upregulated and 579 were downregulated. The top highly expressed EAT circRNAs corresponded to genes involved in inflammation and cell proliferation, including SUPT5H, CCDC62, DPY19L1P1, RASGRP1, AP3S1, CGNL1, KAT2B, BNIP2, and SACS. The top three circRNAs with higher FCs (fold changes) were hsa_circ_0099634, hsa_circ_0000932 and hsa_circ_0097669 (FC=25.6), while lower FCs were identified in hsa_circ_0135289, hsa_circ_0098155 and hsa_circ_0079672. A network involving these noncoding RNAs and mRNAs was also constructed to predict their potential biological functions in the pathology of AF.

conclusionsOur study provided novel insight into EAT's roles in AF and proposed interactions, including possible mediators.