Large extracellular vesicles in the left atrial appendage in patients with atrial fibrillation-the missing link?

Andreas Zietzer1,2, Baravan Al-Kassou3, Paul Jamme3

  • 1Medical Department II, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany. andreas.zietzer@ukbonn.de.

Insights

Permanent atrial fibrillation (AF) is linked to more platelet-derived large extracellular vesicles (lEVs) in the left atrial appendage. These lEVs may contribute to thrombus formation, increasing stroke risk.

Area of Science:

  • Cardiovascular Medicine
  • Hematology
  • Molecular Biology

Background:

  • Atrial fibrillation (AF) is a common arrhythmia linked to thrombus formation and stroke.
  • Large extracellular vesicles (lEVs) can promote coagulation, with their origin influencing function.
  • Understanding AF's impact on lEV subtypes is crucial for stroke prevention strategies.

Purpose of the Study:

  • To investigate how different types of atrial fibrillation (AF) affect large extracellular vesicle (lEV) subtypes in specific atrial locations.
  • To determine the association between AF, lEV levels, and potential pro-coagulant mechanisms.

Main Methods:

  • Collected blood samples from the right atrium, left atrium, and left atrial appendage of 58 patients (permanent AF, non-permanent AF, no AF history).
  • Utilized flow cytometry to analyze the origin of lEVs.
  • Conducted in vitro studies on platelet activation and its effect on lEVs and endothelial cell migration.

Main Results:

  • Permanent AF patients showed significantly higher proportions of platelet-derived lEVs in the left atrial appendage compared to non-permanent AF patients.
  • Patients with atrial fibrillation (regardless of permanence) had elevated platelet-derived lEVs in the left atrial appendage.
  • In vitro, activated platelet-derived lEVs (containing miR-222-3p and miR-223-3p) reduced endothelial cell migration.

Conclusions:

  • Permanent AF is associated with increased platelet-derived lEVs in the left atrial appendage.
  • These lEVs may play a role in the thrombus formation observed in the left atrial appendage during AF.
  • Further research into lEVs could offer new therapeutic targets for AF-related stroke.