Kinetics Analysis of Circulating MicroRNAs Unveils Markers of Failed Myocardial Reperfusion

Jose Coelho-Lima1, Ashfaq Mohammed2, Suzanne Cormack2

  • 1Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

Clinical Chemistry
|November 2, 2019
PubMed
Abstract

Insights

Circulating microRNAs (miRNAs) like miR-1 and miR-133b increase after primary percutaneous coronary intervention (PPCI) in ST-elevation myocardial infarction (STEMI) patients. Elevated levels are linked to microvascular obstruction (MVO) and poorer left ventricular function recovery.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biomarker Discovery

Background:

  • Microvascular obstruction (MVO) affects 50% of ST-elevation myocardial infarction (STEMI) patients post-primary percutaneous coronary intervention (PPCI).
  • MVO, detectable by cardiac magnetic resonance (CMR), has significant prognostic implications but is not routinely assessed.
  • Investigating circulating microRNAs (miRNAs) post-PPCI may reveal novel biomarkers for MVO.

Purpose of the Study:

  • To examine the kinetics of circulating miRNAs following PPCI in STEMI patients.
  • To determine the association between specific miRNAs and the presence of MVO.
  • To explore the relationship between miRNA levels and left ventricular (LV) functional recovery.

Main Methods:

  • Next-generation sequencing screened 2083 miRNAs in plasma from STEMI patients with and without MVO.
  • Two candidate miRNAs were quantified using reverse transcription and quantitative PCR at multiple time points within 3 hours post-PPCI.
  • MiRNA levels were measured in a validation cohort (n=50) with CMR imaging to assess MVO and LV function at 3 months.

Main Results:

  • miR-1 and miR-133b showed rapid release kinetics post-PPCI, with enrichment in circulating microparticles.
  • A secondary miR-1 peak (90-180 min) correlated with increased microvascular resistance.
  • Elevated miR-1 and miR-133b levels at 90 min post-PPCI were significantly associated with MVO (3-fold and 4.4-fold higher, respectively).
  • Higher miR-1 levels at 90 min post-PPCI were linked to worse LV functional recovery at 3 months.

Conclusions:

  • Circulating miR-1 and miR-133b levels rise within 3 hours of PPCI in STEMI patients.
  • These miRNAs are positively associated with MVO, a key indicator of reperfusion injury.
  • Elevated miR-1 and miR-133b levels may predict impaired left ventricular functional recovery post-PPCI.