Neutrophil Extracellular Traps in ST-Segment Elevation Myocardial Infarction: Reduced by Tocilizumab and Associated
Kristine Mørk Kindberg1,2, Kaspar Broch3,4, Geir Øystein Andersen5
1Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevaal, Oslo, Norway.
JACC. Advances
|September 9, 2024
Summary
Tocilizumab treatment reduced neutrophil extracellular traps (NETs) in ST-segment elevation myocardial infarction (STEMI) patients. This reduction in NETs was associated with improved myocardial salvage, suggesting a potential therapeutic mechanism.
Area of Science:
- Cardiology
- Immunology
- Biochemistry
Background:
- Interleukin-6 receptor inhibition with tocilizumab demonstrates improved myocardial salvage in ST-segment elevation myocardial infarction (STEMI) patients.
- Reduced levels of neutrophil extracellular traps (NETs) may contribute to the therapeutic effects of tocilizumab.
Purpose of the Study:
- To evaluate tocilizumab's effect on NETs in STEMI patients.
- To investigate the association between NETs and myocardial injury.
Main Methods:
- The ASSAIL-MI substudy randomized 199 STEMI patients to tocilizumab or placebo.
- NET markers (dsDNA, myeloperoxidase-DNA, H3Cit) were measured at multiple time points.
- Associations between NET markers and myocardial salvage index (MSI) were analyzed.
Main Results:
- Tocilizumab significantly reduced all NET markers compared to placebo at 3-7 days post-treatment (P < 0.04).
- NET-related pathways were downregulated in the tocilizumab group.
- Reduced NET levels partially mediated tocilizumab's beneficial effect on MSI.
Conclusions:
- Tocilizumab effectively reduces NETs in STEMI patients.
- NET reduction by tocilizumab is associated with myocardial injury.
- The therapeutic effect of tocilizumab on myocardial salvage index may be mediated by reduced NETs.
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