Identification of molecular signatures in epicardial adipose tissue in heart failure with preserved ejection fraction.

Abstract

The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non-coding RNAs (lncRNAs) in EAT that might modulate HFpEF development. RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n=5) and without HF (control, n=5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real-time PCR (qRT-PCR). Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) of differentially expressed RNAs was performed to predict enriched functions. HFpEF patients had higher EAT thickness and NT-proBNP levels than the control group. A total of 64471 transcripts were detected including 35395 protein-coding sequences, corresponding to 16854 genes in EAT. RNA-seq identified a total of 741 dysregulated mRNA transcripts (394 up-regulated and 347 down-regulated) and 334 differentially expressed lncRNA transcripts (222 up-regulated and 112 down-regulated) in the HFpEF group compared with the control group (P<0.05). qRT-PCR analysis confirmed that two lncRNAs ENST00000561775 (P=0.0194) and ENST00000519093 (P=0.027) and an mRNA POSTN (P=0.003) were differentially expressed. Functional enrichment analysis of the differentially expressed mRNAs suggested their potential roles in immune response involving cytokine interaction and chemokine signalling. We are the first group to report on the lncRNA and mRNA landscape in EAT in HFpEF patients. Our study suggests the possible role of lncRNAs in EAT.