The N-6 methyladenosine dynamics in STEMI and the effect of IL-6 inhibition - a hypothesis generating sub-study of the ASSAIL-MI trial
BackgroundEpitranscriptomics, with m6A as the most prevalent in mammals, is a novel treatment target for inflammatory diseases, including cardiovascular diseases. However, little is known about m6A RNA-regulation during myocardial infarction (MI).MethodsIn this explorative sub-study of the ASSAIL-MI...
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Frontiers Media S.A.
2025-06-01
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| author | Tuva B. Dahl Tuva B. Dahl Ana Quiles-Jiménez Kaspar Broch Kaspar Broch Anne Kristine Anstensrud Anne Kristine Anstensrud Lars Gullestad Lars Gullestad Lars Gullestad Geir Ø. Andersen Geir Ø. Andersen Ola Kleveland Jonas Øgaard Jonas Øgaard Vigdis Bjerkeli Vigdis Bjerkeli Azita Rashidi Kuan Yang Kirsten B. Holven Kirsten B. Holven Pål Aukrust Magnar Bjørås Magnar Bjørås Camilla Huse Camilla Huse Camilla Huse Bente Halvorsen Bente Halvorsen |
| author_facet | Tuva B. Dahl Tuva B. Dahl Ana Quiles-Jiménez Kaspar Broch Kaspar Broch Anne Kristine Anstensrud Anne Kristine Anstensrud Lars Gullestad Lars Gullestad Lars Gullestad Geir Ø. Andersen Geir Ø. Andersen Ola Kleveland Jonas Øgaard Jonas Øgaard Vigdis Bjerkeli Vigdis Bjerkeli Azita Rashidi Kuan Yang Kirsten B. Holven Kirsten B. Holven Pål Aukrust Magnar Bjørås Magnar Bjørås Camilla Huse Camilla Huse Camilla Huse Bente Halvorsen Bente Halvorsen |
| author_sort | Tuva B. Dahl |
| collection | DOAJ |
| description | BackgroundEpitranscriptomics, with m6A as the most prevalent in mammals, is a novel treatment target for inflammatory diseases, including cardiovascular diseases. However, little is known about m6A RNA-regulation during myocardial infarction (MI).MethodsIn 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 m6A sites were analyzed using human m6A single nucleotide resolution microarray analysis. mRNA levels were analyzed using RNA sequencing analysis.ResultsCompared with controls, patients with STEMI had a strikingly different pattern of m6A deposition. In total, 845 m6A 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 m6A 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 m6A deposition.ConclusionsIn this hypothesis generating study, m6A deposition differs STEMI patients and healthy controls. The m6A 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 post-transcriptional regulation of RNA is involved in the immune response during STEMI, highlighting its potential as a target for therapy in MI. |
| format | Article |
| id | doaj-art-57ede231e5544e97b6c7b350baff392e |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-57ede231e5544e97b6c7b350baff392e2025-08-20T03:24:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15323251532325The N-6 methyladenosine dynamics in STEMI and the effect of IL-6 inhibition - a hypothesis generating sub-study of the ASSAIL-MI trialTuva B. Dahl0Tuva B. Dahl1Ana Quiles-Jiménez2Kaspar Broch3Kaspar Broch4Anne Kristine Anstensrud5Anne Kristine Anstensrud6Lars Gullestad7Lars Gullestad8Lars Gullestad9Geir Ø. Andersen10Geir Ø. Andersen11Ola Kleveland12Jonas Øgaard13Jonas Øgaard14Vigdis Bjerkeli15Vigdis Bjerkeli16Azita Rashidi17Kuan Yang18Kirsten B. Holven19Kirsten B. Holven20Pål Aukrust21Magnar Bjørås22Magnar Bjørås23Camilla Huse24Camilla Huse25Camilla Huse26Bente Halvorsen27Bente Halvorsen28Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, NorwayDepartment of Acute Medicine, Oslo University Hospital, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, NorwayDepartment of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, NorwayK. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, NorwayDepartment of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, NorwayFaculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, NorwayK. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, NorwayFaculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Cardiology, Oslo University Hospital Ullevål, Oslo, NorwayDepartment of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevål, Oslo, NorwayClinic of Cardiology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, NorwayNorwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, NorwayFaculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway0Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway1National Advisory Unit on Familial Hypercholesterolemia, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway2Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway3Department of Microbiology, Oslo University Hospital, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, NorwayFaculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway4Department of Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, NorwayK. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, NorwayBackgroundEpitranscriptomics, with m6A as the most prevalent in mammals, is a novel treatment target for inflammatory diseases, including cardiovascular diseases. However, little is known about m6A RNA-regulation during myocardial infarction (MI).MethodsIn 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 m6A sites were analyzed using human m6A single nucleotide resolution microarray analysis. mRNA levels were analyzed using RNA sequencing analysis.ResultsCompared with controls, patients with STEMI had a strikingly different pattern of m6A deposition. In total, 845 m6A 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 m6A 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 m6A deposition.ConclusionsIn this hypothesis generating study, m6A deposition differs STEMI patients and healthy controls. The m6A 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 post-transcriptional regulation of RNA is involved in the immune response during STEMI, highlighting its potential as a target for therapy in MI.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1532325/fullN6-methyladenosine (m6A)epitranscriptomeRNA methylationSTEMIinflammationtocilizumab |
| spellingShingle | Tuva B. Dahl Tuva B. Dahl Ana Quiles-Jiménez Kaspar Broch Kaspar Broch Anne Kristine Anstensrud Anne Kristine Anstensrud Lars Gullestad Lars Gullestad Lars Gullestad Geir Ø. Andersen Geir Ø. Andersen Ola Kleveland Jonas Øgaard Jonas Øgaard Vigdis Bjerkeli Vigdis Bjerkeli Azita Rashidi Kuan Yang Kirsten B. Holven Kirsten B. Holven Pål Aukrust Magnar Bjørås Magnar Bjørås Camilla Huse Camilla Huse Camilla Huse Bente Halvorsen Bente Halvorsen The N-6 methyladenosine dynamics in STEMI and the effect of IL-6 inhibition - a hypothesis generating sub-study of the ASSAIL-MI trial Frontiers in Immunology N6-methyladenosine (m6A) epitranscriptome RNA methylation STEMI inflammation tocilizumab |
| title | The N-6 methyladenosine dynamics in STEMI and the effect of IL-6 inhibition - a hypothesis generating sub-study of the ASSAIL-MI trial |
| title_full | The N-6 methyladenosine dynamics in STEMI and the effect of IL-6 inhibition - a hypothesis generating sub-study of the ASSAIL-MI trial |
| title_fullStr | The N-6 methyladenosine dynamics in STEMI and the effect of IL-6 inhibition - a hypothesis generating sub-study of the ASSAIL-MI trial |
| title_full_unstemmed | The N-6 methyladenosine dynamics in STEMI and the effect of IL-6 inhibition - a hypothesis generating sub-study of the ASSAIL-MI trial |
| title_short | The N-6 methyladenosine dynamics in STEMI and the effect of IL-6 inhibition - a hypothesis generating sub-study of the ASSAIL-MI trial |
| title_sort | n 6 methyladenosine dynamics in stemi and the effect of il 6 inhibition a hypothesis generating sub study of the assail mi trial |
| topic | N6-methyladenosine (m6A) epitranscriptome RNA methylation STEMI inflammation tocilizumab |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1532325/full |
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