Study of Plasma miRNAs and Microparticle miRNAs in Severe Forms of Pulmonary Hypertension

J. Oto¹, O. Tura-Ceide², V. Sánchez-López³, J. Osorio², C. Bonjoch², D. Hervás⁴, E. Arellano⁵, P. Medina¹, I. Blanco², V.I. Peinado², R. Otero⁶, J.A. Barberà², * J Oto and O Tura-Ceide have contributed equally to this work.

¹Medical Research Institute Hospital La Fe, Haemostasis, Thrombosis, Atherosclerosis and Vascular Biology Research Group, Valencia, Spain, ²Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Department of Pulmonary Medicine, Barcelona, Spain, ³Institute of Biomedicine of Seville (IBIS)/CSIC/University of Sevilla, Sevilla, Spain, ⁴Medical Research Institute Hospital La Fe, Biostatistics Unit, Valencia, Spain, ⁵Respiratory Diseases Networking Biomedical Research Centre (CIBERES), Madrid, Spain, ⁶Virgen del Rocio University Hospital, Medical Surgical Unit of Respiratory Diseases, Sevilla, Spain

Abstract Number: PB2209

Meeting: ISTH 2020 Congress

Theme: Venous Thromboembolism and Cardioembolism » Post-thrombotic Syndrome

Background: 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 with the miRNeasy Mini kit (Qiagen) and the expression of 179 miRs was quantified using the Human Serum/Plasma Focus, miRCURY LNA miRNA Focus PCR V5 (Qiagen). 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: Fourteen miRs (miR-301a-3p, miR-339-5p, miR-652-3p, miR-331-3p, miR-484, miR-18a-5p, miR-127-3p, miR-133a-3p, miR-629-5p, miR-361-5p, miR-200c-3p, miR-144-5p, miR-34a-5p and miR-10b-5p) contained in MPs and 4 plasma miRs (miR-133a-3p, miR-28-5p, miR-26a-5p and miR103a-3p) were differentially expressed among the different groups. Among them, miR-133a-3p 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. Funding sources: Instituto de Salud Carlos III (PI15/01085, PI15/00582, CPII15/00002 and CP17/00114), SETH and SEPAR 164/2016.

To cite this abstract in AMA style:

Oto J, Tura-Ceide O, Sánchez-López V, Osorio J, Bonjoch C, Hervás D, Arellano E, Medina P, Blanco I, Peinado VI, Otero R, Barberà JA, *. Study of Plasma miRNAs and Microparticle miRNAs in Severe Forms of Pulmonary Hypertension [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/study-of-plasma-mirnas-and-microparticle-mirnas-in-severe-forms-of-pulmonary-hypertension/. Accessed September 21, 2023.

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