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Kinetics Analysis of Circulating MicroRNAs Unveils Markers of Failed Myocardial Reperfusion

Lookup NU author(s): Jose Coelho Lima Junior, Dr Ashfaq Mohammed, Dr Suzanne Cormack, Adnan Ali, Dr Matthew Barter, Dr Alan Bagnall, Professor Simi Ali, Professor David Young, Professor Ioakim Spyridopoulos

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Association for Clinical Chemistry, 2020.

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Abstract

Background: Failed myocardial reperfusion occurs in up to 50% of patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). It is strongly associated with worse clinical outcome but is not routinely screened for. Muscle-enriched microribonucleic acids (miRNAs) levels are deregulated following STEMI. Whether they inform about failed myocardial reperfusion is poorly understood. Our aim was to investigate the release kinetics of miRNAs following PPCI and their association with failed myocardial reperfusion in patient with STEMI. Methods and results: Two candidate miRNAs (miR-1 and miR-133b) were identified following screening of 2,083 miRNAs by next generation sequencing in plasma from STEMI patients with (n=6) and without (n=6) failed myocardial reperfusion or healthy controls (n = 4). Measurements of miR-1 and miR-113b were performed at 13 time points within 3h post-reperfusion in 20 STEMI patients using TaqMan small RNA assays by RT-qPCR. This revealed that miR-1/miR-133b are rapidly released following reperfusion in a monophasic or biphasic pattern. In a ‘validation’ STEMI cohort (n = 50), miR-1 and miR-133b levels at 90min post-PPCI were approximately 3-fold (p = 0.001) and 4.4-fold (p = 0.008) higher in patients with failed myocardial reperfusion as assessed by cardiac resonance cardiac (CMR) imaging, respectively. In addition, miR-1 was particularly elevated in a subgroup of patients with worse left ventricular (LV) functional recovery 3 months post-PPCI. Conclusion: miR-1 and miR-133b levels increase within 3h of PPCI. They are positively associated with failed myocardial reperfusion and worse LV functional recovery post-PPCI.


Publication metadata

Author(s): Coelho-Lima J, Mohammed A, Cormack S, Jones S, Ali A, Panahi P, Barter M, Bagnall A, Ali S, Young D, Spyridopoulos I

Publication type: Article

Publication status: Published

Journal: Clinical Chemistry

Year: 2020

Volume: 66

Issue: 1

Pages: 247-256

Print publication date: 01/01/2020

Online publication date: 31/10/2019

Acceptance date: 17/09/2019

Date deposited: 04/10/2019

ISSN (print): 0009-9147

ISSN (electronic): 1530-8561

Publisher: American Association for Clinical Chemistry

URL: https://doi.org/10.1373/clinchem.2019.308353

DOI: 10.1373/clinchem.2019.308353

PubMed id: 31672851


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