Differential miRNAs in acute spontaneous coronary artery dissection : Pathophysiological insights from a potential biomarker
Lozano-Prieto, Marta (Hospital Universitario de la Princesa (Madrid))
Adlam, David (NIHR Leicester Biomedical Research Centre)
García-Guimaraes, Marcos (Hospital del Mar (Barcelona, Catalunya))
Sanz-García, Ancor (Hospital Universitario de la Princesa (Madrid))
Vera-Tomé, Paula (Hospital Universitario de la Princesa (Madrid))
Rivero, Fernando (Hospital Universitario de la Princesa (Madrid))
Cuesta, Javier (Hospital Universitario de la Princesa (Madrid))
Bastante, Teresa (Hospital Universitario de la Princesa (Madrid))
Baranowska-Clarke, Anna A. (NIHR Leicester Biomedical Research Centre)
Vara, Alicia (Hospital Universitario de la Princesa (Madrid))
Martin-Gayo, Enrique (Hospital Universitario de la Princesa (Madrid))
Vicente-Manzanares, Miguel (Instituto de Biología Molecular y Celular del Cáncer USAL-CSIC)
Martín, Pilar (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Samani, Nilesh J. (NIHR Leicester Biomedical Research Centre)
Sánchez-Madrid, Francisco (Hospital Universitario de la Princesa (Madrid))
Alfonso, Fernando (NIHR Leicester Biomedical Research Centre)
de la Fuente, Hortensia (Hospital Universitario de la Princesa (Madrid))
Universitat Autònoma de Barcelona

Data:	2021
Resum:	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. 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. 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. 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. 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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Spontaneous coronary artery dissection ; MicroRNAs ; Acute myocardial infarction ; Biomarker
Publicat a:	EBioMedicine, Vol. 66 (april 2021) , ISSN 2352-3964

DOI: 10.1016/j.ebiom.2021.103338
PMID: 33866193

9 p, 1.6 MB

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