Genome-wide screening for circRNAs in epicardial adipose tissue of heart failure patients with preserved ejection fraction

Objective: Heart failure with preserved ejection fraction (HFpEF) is a complex cardiovascular syndrome. Along with pro-inflammatory and metabolic factors, epicardial adipose tissue (EAT) is believed to play a key role in the pathogenesis of HFpEF. Studies have increasingly shown a critical role of circRNAs in the development of cardiovascular diseases; however, their role in the pathogenetic mechanism of HFpEF is not well characterized. The objective of this study was to investigate the expression profiles of circRNAs in EAT of HFpEF patients. Methods: Samples of epicardial adipose tissue were obtained from patients with HFpEF (n=5) and patients without heart failure (non-HF; n=5). CircRNA expression profiles were screened using RNA sequencing method. RNA-sequencing results were confirmed by qRT-PCR analysis. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed on the differentially expressed circRNAs. Results: A total of 131 circRNAs were differentially expressed between HFpEF and non-HF groups (77 upregulated and 54 downregulated). Among these, hsa_circ_0118464 corresponding to HECW2 gene which showed the highest fold-change was assessed by qRT-PCR, and the outcome was consistent with RNA-sequencing results. The differentially expressed circRNAs corresponded to genes mainly involved in regulation of cellular and metabolic processes. Conclusion: This study provides the expression profile of circRNAs in EAT of HFpEF patients and the associated molecular mechanism. Our findings may provide insight into diagnostic markers and therapeutic targets in the context of HFpEF.