ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Clinical and Translational Cardiovascular Medicine
Functional Autoantibodies and Coronary Microvascular Obstruction in STEMI: A Translational Link Between Immune Mechanisms and Prognostic Outcomes
Laura Iop 1
Giovanni Civieri 1
Giacomo Bernava 1
Nicola Meynardi 1
Marta Vadori 1
Giulia Masiero 2
Marika Martini 1
Nicola Morat 1
Donatella Tansella 3
Sabino Iliceto 4
Emanuele Cozzi 1
Francesco Tona 1
1. University of Padua, Padua, Italy
2. Azienda Ospedale Universita Padova, Padua, Italy
3. Heart Center, Mater Dei Hospital, Bari, Italy
4. Universita LUM Giuseppe Degennaro, Casamassima, Italy
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Abstract
Background: Despite timely primary percutaneous coronary intervention, coronary microvascular obstruction (CMVO) continues to limit myocardial reperfusion and worsen prognosis in patients with ST-elevation myocardial infarction (STEMI). Agonistic autoantibodies targeting the angiotensin II type 1 (AT1R) and endothelin-1 type A (ETAR) receptors have been associated with CMVO, but whether they directly contribute to microvascular injury remains unclear. Methods: We prospectively enrolled 287 STEMI patients and evaluated CMVO, left ventricular remodeling, and major adverse cardiovascular events during a median follow-up of 460 days. Immunoglobulins were isolated from a subset of patients with the highest AT1R-AA and ETAR-AA titers and from seronegative controls. Human cardiac microvascular endothelial cells were exposed to patient-derived or control immunoglobulins, with or without pharmacological receptor blockade. Results: Patients with higher autoantibody titers showed a greater prevalence of CMVO and worse clinical outcomes. In vitro, immunoglobulins from seropositive patients rapidly induced endothelial dysfunction, characterized by cytoskeletal disorganization, junctional disruption, endothelial activation, and increased mitochondrial oxidative stress. These alterations were most pronounced at 24 hours and progressed to reduced cell viability and increased cytotoxicity at 48 hours. Immunoglobulins from seronegative controls had no relevant effects. Blockade of AT1R and ETAR significantly mitigated endothelial injury and oxidative stress. Conclusions: Agonistic autoantibodies against AT1R and ETAR directly damage coronary microvascular endothelium and reproduce key features of CMVO observed in STEMI patients. These findings support a clinically relevant, immune-mediated mechanism of microvascular injury and suggest that receptor antagonism represents a biologically plausible, receptor-dependent mechanism warranting further investigation as a potential microvascular protective strategy in high-risk STEMI patients.
Summary
Keywords
AT1 receptor, Autoantibodies, coronary microcirculation, endothelialdysfunction, ETA receptor, Receptor antagonists, ST-elevation myocardial infarction
Received
06 November 2025
Accepted
02 February 2026
Copyright
© 2026 Iop, Civieri, Bernava, Meynardi, Vadori, Masiero, Martini, Morat, Tansella, Iliceto, Cozzi and Tona. 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: Francesco Tona
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.