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

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...

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Autores principales: Lozano-Prieto, Marta, Adlam, David, García-Guimaraes, Marcos, Sanz-García, Ancor, Vera-Tomé, Paula, Rivero, Fernando, Cuesta, Javier, Bastante, Teresa, Baranowska-Clarke, Anna A., Vara, Alicia, Martin-Gayo, Enrique, Vicente-Manzanares, Miguel, Martín, Pilar, Samani, Nilesh J, Sánchez-Madrid, Francisco, Alfonso, Fernando, de la Fuente, Hortensia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079473/
https://www.ncbi.nlm.nih.gov/pubmed/33866193
http://dx.doi.org/10.1016/j.ebiom.2021.103338
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author Lozano-Prieto, Marta
Adlam, David
García-Guimaraes, Marcos
Sanz-García, Ancor
Vera-Tomé, Paula
Rivero, Fernando
Cuesta, Javier
Bastante, Teresa
Baranowska-Clarke, Anna A.
Vara, Alicia
Martin-Gayo, Enrique
Vicente-Manzanares, Miguel
Martín, Pilar
Samani, Nilesh J
Sánchez-Madrid, Francisco
Alfonso, Fernando
de la Fuente, Hortensia
author_facet Lozano-Prieto, Marta
Adlam, David
García-Guimaraes, Marcos
Sanz-García, Ancor
Vera-Tomé, Paula
Rivero, Fernando
Cuesta, Javier
Bastante, Teresa
Baranowska-Clarke, Anna A.
Vara, Alicia
Martin-Gayo, Enrique
Vicente-Manzanares, Miguel
Martín, Pilar
Samani, Nilesh J
Sánchez-Madrid, Francisco
Alfonso, Fernando
de la Fuente, Hortensia
author_sort Lozano-Prieto, Marta
collection PubMed
description 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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spelling pubmed-80794732021-04-29 Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker Lozano-Prieto, Marta Adlam, David García-Guimaraes, Marcos Sanz-García, Ancor Vera-Tomé, Paula Rivero, Fernando Cuesta, Javier Bastante, Teresa Baranowska-Clarke, Anna A. Vara, Alicia Martin-Gayo, Enrique Vicente-Manzanares, Miguel Martín, Pilar Samani, Nilesh J Sánchez-Madrid, Francisco Alfonso, Fernando de la Fuente, Hortensia EBioMedicine Research Paper 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. Elsevier 2021-04-15 /pmc/articles/PMC8079473/ /pubmed/33866193 http://dx.doi.org/10.1016/j.ebiom.2021.103338 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Lozano-Prieto, Marta
Adlam, David
García-Guimaraes, Marcos
Sanz-García, Ancor
Vera-Tomé, Paula
Rivero, Fernando
Cuesta, Javier
Bastante, Teresa
Baranowska-Clarke, Anna A.
Vara, Alicia
Martin-Gayo, Enrique
Vicente-Manzanares, Miguel
Martín, Pilar
Samani, Nilesh J
Sánchez-Madrid, Francisco
Alfonso, Fernando
de la Fuente, Hortensia
Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker
title Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker
title_full Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker
title_fullStr Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker
title_full_unstemmed Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker
title_short Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker
title_sort differential mirnas in acute spontaneous coronary artery dissection: pathophysiological insights from a potential biomarker
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079473/
https://www.ncbi.nlm.nih.gov/pubmed/33866193
http://dx.doi.org/10.1016/j.ebiom.2021.103338
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