An extracellular vesicle epitope profile is associated with acute myocardial infarction

J Cell Mol Med. 2020 Sep;24(17):9945-9957. doi: 10.1111/jcmm.15594. Epub 2020 Jul 14.

Abstract

The current standard biomarker for myocardial infarction (MI) is high-sensitive troponin. Although powerful in clinical setting, search for new markers is warranted as early diagnosis of MI is associated with improved outcomes. Extracellular vesicles (EVs) attracted considerable interest as new blood biomarkers. A training cohort used for diagnostic modelling included 30 patients with STEMI, 38 with stable angina (SA) and 30 matched-controls. Extracellular vesicle concentration was assessed by nanoparticle tracking analysis. Extracellular vesicle surface-epitopes were measured by flow cytometry. Diagnostic models were developed using machine learning algorithms and validated on an independent cohort of 80 patients. Serum EV concentration from STEMI patients was increased as compared to controls and SA. EV levels of CD62P, CD42a, CD41b, CD31 and CD40 increased in STEMI, and to a lesser extent in SA patients. An aggregate marker including EV concentration and CD62P/CD42a levels achieved non-inferiority to troponin, discriminating STEMI from controls (AUC = 0.969). A random forest model based on EV biomarkers discriminated the two groups with 100% accuracy. EV markers and RF model confirmed high diagnostic performance at validation. In conclusion, patients with acute MI or SA exhibit characteristic EV biomarker profiles. EV biomarkers hold great potential as early markers for the management of patients with MI.

Keywords: ST-segment elevation myocardial infarction; acute myocardial infarction; biomarker; coronary artery disease; extracellular vesicles; machine learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / metabolism
  • Acute Coronary Syndrome / pathology
  • Aged
  • Angina, Stable / blood*
  • Angina, Stable / genetics
  • Angina, Stable / pathology
  • Biomarkers / blood*
  • CD40 Antigens / blood
  • Cohort Studies
  • Epitope Mapping
  • Epitopes / blood*
  • Epitopes / genetics
  • Extracellular Vesicles / genetics*
  • Female
  • Humans
  • Integrin alpha2 / blood
  • Male
  • Middle Aged
  • P-Selectin / blood
  • Percutaneous Coronary Intervention
  • Platelet Endothelial Cell Adhesion Molecule-1 / blood
  • Platelet Glycoprotein GPIb-IX Complex / genetics
  • ST Elevation Myocardial Infarction / blood*
  • ST Elevation Myocardial Infarction / genetics
  • ST Elevation Myocardial Infarction / pathology

Substances

  • Biomarkers
  • CD40 Antigens
  • Epitopes
  • ITGA2B protein, human
  • Integrin alpha2
  • P-Selectin
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Platelet Glycoprotein GPIb-IX Complex