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Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker

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posted on 2021-12-21, 09:27 authored by M Lozano-Prieto, D Adlam, M García-Guimaraes, A Sanz-García, P Vera-Tomé, F Rivero, J Cuesta, T Bastante, AA Baranowska-Clarke, A Vara, E Martin-Gayo, M Vicente-Manzanares, P Martín, NJ Samani, F Sánchez-Madrid, F Alfonso, H de la Fuente
Background: Spontaneous Coronary Artery Dissection (SCAD) is an important cause of acute coronary syndromes, particularly in young to middle-aged women. Differentiating acute SCAD from coronary atherothrombosis remains a major clinical challenge. Methods: A case-control study was used to explore the usefulness of circulating miRNAs to discriminate both clinical entities. The profile of miRNAs was evaluated using an unbiased human RT-PCR platform and confirmed using individual primers. miRNAs were evaluated in plasma samples from acute SCAD and atherothrombotic acute myocardial infarction (AT-AMI) from two independent cohorts; discovery cohort (SCAD n = 15, AT-AMI n = 15), and validation cohort (SCAD n = 11, AT-AMI n = 41) with 9 healthy control subjects. Plasma levels of IL-8, TGFB1, TGBR1, Endothelin-1 and MMP2 were analysed by ELISA assays. Findings: From 15 differentially expressed miRNAs detected in cohort 1, we confirmed in cohort 2 the differential expression of 4 miRNAs: miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p, whose expression was higher in SCAD compared to AT-AMI. The combined expression of these 4 miRNAs showed the best predictive value to distinguish between both entities (AUC: 0.879, 95% CI 0.72–1.0) compared to individual miRNAs. Functional profiling of target genes identified an association with blood vessel biology, TGF-beta pathway and cytoskeletal traction force. ELISA assays showed high plasma levels of IL-8, TGFB1, TGFBR1, Endothelin-1 and MMP2 in SCAD patients compared to AT-AMI. Interpretation: We present a novel signature of plasma miRNAs in patients with SCAD. miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p discriminate SCAD from AT-AMI patients and also shed light on the pathological mechanisms underlying this condition. Funding: Spanish Ministry of Economy and Competitiveness (MINECO): Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV). Fundación BBVA a equipos de Investigación Científica 2018 and from Caixa Banking Foundation under the project code HR17-00016 to F.S.M. Instituto de Salud Carlos III (AES 2019): PI19/00565 to F.R, PI19/00545 to P.M. CAM (S2017/BMD-3671-INFLAMUNE-CM) from Comunidad de Madrid to FSM and PM. The UK SCAD study was supported by BeatSCAD, the British Heart Foundation (BHF) PG/13/96/30608 the NIHR rare disease translational collaboration and the Leicester NIHR Biomedical Research Centre.

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Citation

Marta Lozano-Prieto, David Adlam, Marcos García-Guimaraes, Ancor Sanz-García, Paula Vera-Tomé, Fernando Rivero, Javier Cuesta, Teresa Bastante, Anna A. Baranowska-Clarke, Alicia Vara, Enrique Martin-Gayo, Miguel Vicente-Manzanares, Pilar Martín, Nilesh J Samani, Francisco Sánchez-Madrid, Fernando Alfonso, Hortensia de la Fuente, Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker, EBioMedicine, Volume 66, 2021, https://doi.org/10.1016/j.ebiom.2021.103338.

Author affiliation

Department of Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

EBioMedicine

Volume

66

Pagination

103338

Publisher

Elsevier

issn

2352-3964

eissn

2352-3964

Acceptance date

2021-03-25

Copyright date

2021

Available date

2021-04-15

Spatial coverage

Netherlands

Language

eng

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