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

EBioMedicine. 2021 Apr:66:103338. doi: 10.1016/j.ebiom.2021.103338. Epub 2021 Apr 15.

Abstract

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.

Keywords: Acute myocardial infarction; Biomarker; Spontaneous coronary artery dissection; microRNAs.

MeSH terms

  • Adult
  • Biomarkers*
  • Case-Control Studies
  • Circulating MicroRNA
  • Coronary Vessel Anomalies / diagnosis
  • Coronary Vessel Anomalies / etiology*
  • Coronary Vessel Anomalies / metabolism
  • Coronary Vessel Anomalies / physiopathology*
  • Diagnosis, Differential
  • Disease Susceptibility
  • Female
  • Gene Expression Regulation*
  • Humans
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / etiology
  • Myocardial Infarction / metabolism
  • RNA Interference
  • RNA, Messenger
  • ROC Curve
  • Vascular Diseases / congenital*
  • Vascular Diseases / diagnosis
  • Vascular Diseases / etiology
  • Vascular Diseases / metabolism
  • Vascular Diseases / physiopathology

Substances

  • Biomarkers
  • Circulating MicroRNA
  • MicroRNAs
  • RNA, Messenger

Supplementary concepts

  • Coronary Artery Dissection, Spontaneous