ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1532325
The N-6 methyladenosine (m 6 A) dynamics in STEMI and the effect of IL-6 inhibition -a hypothesis generating sub-study of the ASSAIL-MI trial
Provisionally accepted
Tuva Dahl1*
Ana Quiles-Jiménez1Kaspar Broch1Anne Kristine Anstensrud1Lars Gullestad1Øystein Andersen1Ola Kleveland2
Jonas Øgaard1Vigdis Bjerkeli3Azita Rashidi1Kuan Yang1
Kirsten B Holven1
Pål Aukrust1Magnar Bjørås4
Camilla Huse1
Bente Halvorsen1- 1Oslo University Hospital, Oslo, Norway
- 2St Olav's University Hospital, Trondheim, Sør-Trøndelag, Norway
- 3University of Oslo, Oslo, Oslo, Norway
- 4NTNU, Trondheim, Sør-Trøndelag, Norway
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Background: Epitranscriptomics, with m 6 A as the most prevalent in mammals, is a novel treatment target for inflammatory diseases, including cardiovascular diseases. However, little is known about m 6 A RNA-regulation during myocardial infarction (MI).In this explorative sub-study of the ASSAIL-MI trial, we used whole blood samples from patients with acute ST-elevation MI (STEMI) (n=6) at admission and after 3-7 days, and from healthy control subjects (n=3). RNA was isolated, and m 6 A sites were analyzed using human m 6 A single nucleotide resolution microarray analysis. mRNA levels were analysed using RNA sequencing analysis.Results: Compared with controls, patients with STEMI had a strikingly different pattern of m 6 A deposition. In total, 845 m 6 A methylation sites in whole blood RNA were hypomethylated and 36 were hypermethylated compared with controls. Of the hypomethylated transcripts, 194 transcripts were lower expressed, while 197 transcripts were higher expressed. The m 6 A pattern changed from an overall hypomethylation at admission to an overall hypermethylation 3-7 day after admission. Anti-inflammatory treatment with tocilizumab further altered the m 6 A deposition.In this hypothesis generating study, m 6 A deposition differs STEMI patients and healthy controls. The m 6 A pattern changes over the course of 3-7 days. This response is, at least to some degree, is modulated by blocking the IL-6 receptor. Our data may suggest that this posttranscriptional regulation of RNA is involved in the immune response during STEMI, highlighting its potential as a target for therapy in MI.
Keywords: N6-methyladenosine (m 6 A), epitranscriptome, RNA methylation, STEMI, Inflammation, tocilizumab
Received: 21 Nov 2024; Accepted: 22 May 2025.
Copyright: © 2025 Dahl, Quiles-Jiménez, Broch, Anstensrud, Gullestad, Andersen, Kleveland, Øgaard, Bjerkeli, Rashidi, Yang, Holven, Aukrust, Bjørås, Huse and Halvorsen. 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: Tuva Dahl, Oslo University Hospital, Oslo, Norway
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