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Untensed fibronectin fibers: a novel hallmark of microthrombi

Arnaud Miéville1, Petra Wolint2, Nikola Cesarovic2,3

  • 1Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, Institute of Translational Medicine, ETH Zürich, Zürich, Switzerland.

Frontiers in Cardiovascular Medicine
|August 27, 2025
PubMed
Abstract

Insights

Loss of fibronectin fiber tension is a key feature of microthrombi in Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA). The peptide FnBPA5 can detect this physical signature, aiding microthrombi diagnosis.

Area of Science:

  • Cardiovascular Medicine
  • Biomaterials Science
  • Molecular Imaging

Background:

  • Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) accounts for up to 15% of acute myocardial infarction cases, presenting diagnostic challenges.
  • Microthrombi are implicated in MINOCA, but their detection is difficult due to the omnipresence of components like fibronectin.
  • Fibronectin's distinct physical states (stretched vs. untensed) offer potential as diagnostic and therapeutic targets.

Purpose of the Study:

  • To investigate fibronectin fiber tension as a biomarker for microthrombi in MINOCA.
  • To evaluate the efficacy of the peptide FnBPA5 in detecting microthrombi based on fibronectin's physical state.

Main Methods:

  • Utilized a pig model of autologous microthrombi-induced MINOCA.
  • Employed the peptide FnBPA5, which selectively binds to untensed fibronectin fibers.
  • Assessed fibronectin fiber tension in microthrombi before and after MINOCA onset.

Main Results:

  • Loss of fibronectin fiber tension was identified as a novel characteristic of microthrombi in the MINOCA model.
  • Fibronectin fibers in the surrounding healthy myocardium remained highly stretched.
  • FnBPA5 effectively visualized fibronectin's physical signature, distinguishing microthrombi from healthy tissue.

Conclusions:

  • Fibronectin fiber untension is a unique mechanical biomarker for microthrombi detection in MINOCA.
  • FnBPA5 demonstrates high specificity for detecting microthrombi by targeting untensed fibronectin.
  • FnBPA5 holds promise for advanced microthrombi detection and mechano-therapeutic strategies.
Keywords:
MINOCAextracellular matrix (ECM)fibronectinmechanobiologymyocardial infarction

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