Non-invasive approach for evaluation of CTEPH using extracellular vesicle-associated small non-coding RNA

The aim of this study was to determine whether extracellular vesicle (EV)-associated small non-coding RNAs (sncRNAs) have potential as biomarkers for chronic thromboembolic pulmonary hypertension (CTEPH). EVs were isolated using different methods from serum of 23 CTEPH patients and 23 controls. EV-associated RNAs were analysed by next-generation sequencing using the TrueQuant method for molecular barcoding, and differentially expressed sncRNAs were validated by qRT-PCR. We identified 18 miRNAs and 21 piRNAs or piRNA clusters that were differentially expressed in CTEPH patients compared with the control group. Bioinformatic analysis predicted a contribution of these piRNAs to the progression of cardiac and vascular remodelling. Furthermore, the expression levels of DQ593039 correlated with clinically meaningful parameters such as mean pulmonary arterial pressure, pulmonary vascular resistance, right ventricular systolic pressure, and levels of N-terminal pro-brain natriuretic peptide. In summary, EV-associated piRNA DQ593039 shows promise as biomarker and may be a potential therapeutic target for CTEPH. Small RNA profiles of CTEPH patients and age- and sex-matched healthy controls were generated by deep sequencing, in triplicate, using Illumina NextSeq 500.