Expression profiles and functional analysis of tRNA-derived small RNAs in epicardial adipose tissue of patients with heart failure.

ABSTRACT

BACKGROUND: Heart failure is considered an epidemic disease in the modern world. Since it presents as a multifactorial, systemic disease, a comprehensive understanding of the underlying mechanism is essential. Epicardial adipose tissue (EAT) is increasingly recognized to be metabolically active and is able to secrete myriad bioactive molecules, including exosomes carrying tRNA-derived small RNAs (tsRNAs). Mounting evidence has suggested that these specific tsRNAs dynamically impact fundamental cellular processes, but no studies have focused on the influence of tsRNA in EAT on cardiac dysfunction. METHODS: To investigate the regulatory mechanism of tsRNAs of EAT associated with HF, we collected EAT from HF (n = 5) patients and controls (n = 5) and used a combination of RNA sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and bioinformatics to screen the expression profiles of tsRNAs in HF. RESULTS: We ultimately identified an expression profile of 343 tsRNAs in EAT. Of those, a total of 24 tsRNAs were significantly differentially expressed between HF and controls 17 were upregulated and 7 were downregulated (fold change >1.5, p < 0.05). Four tsRNAs (tiRNA-Pro-TGG-001, tRF-Met-CAT-002, tRF-Tyr-GTA-010 and tRF-Tyr-GTA-011) were randomly selected and validated by qRT-PCR. Bioinformatics analyses revealed a dense interaction of target genes between tRF-Tyr-GTA-010 and tRF-Tyr-GTA-011. Based on functional analysis, these two tRFs might play a protective role by regulating sphingolipid and adrenergic signaling pathways by targeting genes mainly contributing to calcium ion transport. CONCLUSIONS: Our study profiled tsRNA expression in EAT with HF and identified a comprehensive dimension of potential target genes and tsRNA-mRNA interactions.

The development of heart failure involves a complex mechanistic network, which until now, has not been clarified.Excess epicardial adipose tissue may promote heart failure via unknown mechanisms.Our current study profiled transfer RNAs expression in epicardial adipose tissue with heart failure and identified a comprehensive dimension of potential target genes and transfer RNAs -mRNA interactions for the pathogenesis of deterioration in cardiac function.