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MiR-93-5p is a novel predictor of coronary in-stent restenosis
  1. John F O'Sullivan1,2,
  2. Antoinette Neylon1,
  3. Eoin F Fahy1,
  4. Pengyi Yang3,
  5. Catherine McGorrian1,4,
  6. Gavin J Blake1,4
  1. 1 Department of Cardiology, Mater Misericordiae University Hospital, Dublin, Ireland
  2. 2 The University of Sydney - Department of Cardiology, Royal Prince Alfred Hospital; Heart Research Institute, Charles Perkins Centre, Johns Hopkins Drive, The University of Sydney, Sydney, New South Wales, Australia
  3. 3 The University of Sydney - Computational Trans-Regulatory Biology Group, School of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, Australia
  4. 4 School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
  1. Correspondence to Dr John F O'Sullivan, Heart Research Institute, Charles Perkins Centre, Johns Hopkins Drive, The University of Sydney, Sydney, NSW 2050, Australia; john.osullivan{at}sydney.edu.au

Abstract

Aims MicroRNAs (miRNAs), small non-coding RNAs, have been implicated as regulators of multiple phases of atherothrombosis, and some reports have suggested altered levels in coronary artery in-stent restenosis (ISR). We recently demonstrated that miR-93-5 p was able to discriminate between patients with stable coronary artery disease (CAD) and those with no CAD, after adjusting for traditional risk factors (RFs). Thus, we wanted to determine if circulating miRNAs could predict coronary ISR.

Objective To determine if circulating miRNAs have diagnostic capability for determining ISR in a cohort of matched patients with and without ISR.

Approach and results To determine if miRNA plasma levels are elevated in coronary ISR, we conducted a study comprising 78 patients (39 with no ISR and 39 with ISR) and measured plasma miRNAs in each. We then determined the predictive ability of differential miRNAs, adjusting for Framingham Heart Study (FHS) RFs, and stent length and diameter, to discriminate between ISR and no ISR. After correction for multiple testing, two miRNAs—miR425-5p and miR-93-5 p—were differential between patients with ISR and patients without ISR. Only miR-93-5 p remained a strong independent predictor of ISR after correction for FHS RFs (OR 6.30, p=0.008) and FHS RFs plus stent length and diameter (OR 4.80, p=0.02) and improved discriminatory power for ISR over FHS RFs alone in receiver operator characteristic curve analysis.

Conclusion This novel finding that miR-93-5 p independently predicts ISR extends our recent observation that miR-93-5 p predicted CAD after adjustment for traditional CAD RFs. These data suggest further potential diagnostic utility.

  • MicroRNA
  • coronary stent
  • restenosis

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • JFO and AN contributed equally.

  • Contributors JOS and GJB conceived and designed the study, obtained ethics approval and wrote the manuscript. AN collected and processed the samples, analysed the images, consented the patients and wrote the manuscript. CM provided critical insight and helped write the manuscript. EFF analysed the data and helped write the manuscript. PY determined appropriate statistical analysis and performed statistical analysis.

  • Funding This work was supported by a University College Dublin grant awarded to GJB.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval All studies were approved by the Institutional Review Boards of the Mater Misericordiae University Hospitals

  • Provenance and peer review Not commissioned; externally peer reviewed.

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