Exosomal piRNA sequencing reveals differences between heart failure and healthy patients.

Abstract

Heart failure is a leading cause of cardiovascular mortality in industrialized countries. Increasing evidence has highlighted the relationship between noncoding regulatory RNAs, especially microRNAs, and heart failure. However, few studies address the role of piRNAs in heart failure. Therefore, we compared exosomal piRNAs between heart failure patients and healthy volunteers to investigate the role of piRNAs in heart failure. First, exosomes were isolated from the serum of heart failure patients and healthy volunteers. After confirming exosome identity by electron microscopy, nanoparticle analysis, and Western blotting, RNA was extracted from exosomes. The expression of piRNAs was then compared by RNA sequencing and bioinformatics analysis. Serum exosomes from heart failure patients and healthy volunteers were successfully isolated and identified. Serum exosome presence was increased in heart failure patients compared to healthy volunteers. RNA sequencing and bioinformatics analysis revealed that 585 piRNAs were upregulated in heart failure patients, and 4,623 piRNAs were downregulated. Among these piRNAs, has-piR-020009 and has-piR-006426 were the most downregulated. Collectively, a dramatic difference in the expression of piRNAs in serum exosomes of heart failure patients was observed. Altogether, these data suggest that piRNAs are potential biomarkers of heart failure and that serum exosome isolation may provide a clinically relevant source of piRNAs for sequencing analysis.