Differential expression of miRNAs present in plasma and contained within circulating microparticles in precapillary pulmonary hypertension

Abstract

Introduction: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are serious forms of precapillary pulmonary hypertension (PH) with reduced prognosis, despite recent advances in their treatment. Epigenetic mechanisms might be involved in the pathogenesis of these diseases. Aims: To study the epigenetic mechanisms in severe precapillary PH through the identification of dysregulated microRNAs (miRs) contained in circulating plasma microparticles (MPs) and their differential expression with respect to paired total plasma. Methods: Thirty patients with PH and 10 healthy subjects were prospectively recruited. Patients with PH were classified in: PAH, surgical CTEPH and non-surgical CTEPH (n=10/each). Plasma samples were collected and MPs were isolated from all subjects. Total RNA was isolated from both plasma and MPs and the expression of 179 miRs was quantified. Expression levels were normalized with the endogenous and stable miR-425-5p selected using BestRef. Statistical analysis of differentially expressed miRs (in plasma and MPs) among all groups was performed using R (v3.5.0). Results: Patients had severe PH (mPAP 47±11 mmHg, PVR 915±525 dyn·s·cm-5). Fourteen[ro1] miRs contained in MPs (Figure 1) and 4 plasma miRs (Figure 2) were differentially expressed among the different groups. Among them, miR-133a-3pis was found to be dysregulated in both MPs and plasma. Conclusions: Patients with precapillary PH show a differentiated profile of miRs in both plasma and circulating MPs. miR-133a-3p might play a prominent role in PH as it is downregulated in both plasma and MPs in patients with PAH or CTEPH.