ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Thrombosis and Haemostasis
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1627917
This article is part of the Research TopicPrognostic Value of Inflammatory and Thrombotic Biomarkers in Acute Coronary SyndromeView all 5 articles
Untensed Fibronectin Fibers: A Novel Hallmark of Microthrombi
Provisionally accepted
- 1ETH Zürich, Zurich, Switzerland
- 2Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zürich,, Zürich, Switzerland
- 3Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland
- 4Deutsches Herzzentrum der Charite (DHZC), Department of Cardiothoracic and Vascular Surgery, Berlin, Germany, Berlin, Germany
- 5Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland
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MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries) accounts for up to 15% of acute Myocardial Infarction (MI) cases and presents significant diagnostic and therapeutic challenges due to its heterogeneous nature. The specific targeting of microthrombi involved in microthrombi-induced MINOCA with molecule-specific precision has been challenging due to their omnipresence in the bloodstream. Rather than using monoclonal antibodies, we demonstrate here how to target the tensional signature of Fibronectin fibers, which differs significantly between blood clots and the surrounding tissue. Using FnBPA5, a highly specific peptide probe that specifically binds to untensed Fibronectin fibers, as fiber stretching destroys its multivalent binding motif, we identified the loss of Fibronectin fiber tension as a key feature of microthrombi illustrated here in a pig model of autologous microthrombi-induced MINOCA. In contrast, Fibronectin fibers are highly tensed in the healthy heart and in other healthy organs too. These findings highlight FnBPA5's potential to target the physical state of an omnipresent extracellular matrix (ECM) molecule in a blood clot, such that untensed Fibronectin fibers can serve as mechanical biomarker for microthrombi detection in coronary arteries. The peptide's ability to target untensed Fibronectin in microthrombi makes it a promising tool for advanced microthrombi imaging applications and for therapeutic strategies involving the targeted delivery of therapeutic agents.
Keywords: MINOCA, mechanobiology, fibronectin, myocardial infarction, Extracellular Matrix (ECM)
Received: 13 May 2025; Accepted: 24 Jul 2025.
Copyright: © 2025 Miéville, Wolint, Cesarovic, Falk and Vogel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Viola Vogel, Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland
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