Key result
IRAK-M deletion aggravated acute inflammatory response, macrophage activation, and mitochondrial dysfunction following myocardial infarction, with S100A8/A9 acting as a central molecule.
Why the study?
IRAK-M plays an important role in acute MI pathophysiology, but its effects on biological functions and molecular interactions post-MI required further exploration.
Does IRAK-M deletion affect the acute inflammatory response and mitochondrial dysfunction following myocardial infarction?
Does IRAK-M deletion affect the acute inflammatory response and mitochondrial dysfunction following myocardial infarction?
IRAK-M plays an essential regulatory role post-MI by controlling acute inflammatory responses and mediating mitochondrial respiratory function, suggesting it as a potential therapeutic target.
May guide targeted IRAK-M research in post-MI inflammation; leaves open any clinical role pending prospective validation.
Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Interleukin-1 receptor associated kinase (IRAK)-M is a regulator of Toll-like receptor mediated inflammatory responses and plays an important role in the pathophysiologic processes of acute MI. We aimed to explore the effect of IRAK-M on regulating biological function and molecular interactions post-MI through bioinformatics analysis. Datasets from the Gene Expression Omnibus database were used to identify characteristics of IRAK-M expression in MI patients. The expression of IRAK-M was upregulated in MI patients and altered in a time-dependent manner during MI progression. Enrichment analysis showed that biological processes related to inflammatory response and leukocyte activation were markedly activated in MI patients with upregulated IRAK-M. Furthermore, we constructed MI model using wildtype and IRAK-M−/− mice and performed proteomics analysis of infarcted hearts. Functional enrichment of proteomics data indicated that IRAK-M deletion aggravated a series of pathophysiologic functions, such as acute inflammatory response, macrophage activation and mitochondrial dysfunction. S100A8/A9 acted as the central molecule in the above functions based on the protein-protein interaction network and was significantly elevated in IRAK-M−/− infarcted hearts at both the protein and mRNA levels. In conclusion, IRAK-M functioned as an essential regulator in pathophysiologic processes post-MI, exerting effects not only on controlling acute inflammatory responses but also on mediating mitochondrial respiratory function based on integrated bioinformatics analysis. In this study, we combined microarray datasets and a proteomics approach to explore the effect of IRAK-M on mediating biological processes and systemic molecular interactions following MI. Our data firstly showed that IRAK-M is involved in ATP synthesis and mitochondrial respiratory chain complex during MI progression. S100A8/A9 acted as the central molecule in above regulatory network and displayed a tight connection with IRAK-M. The findings provide novel evidence and clues for understanding the complex roles and molecular mechanisms of IRAK-M in the development of MI.
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Chen et al. (2022) studied Myocardial infarction. IRAK-M deletion vs. Wildtype was evaluated on Pathophysiologic functions including acute inflammatory response, macrophage activation and mitochondrial dysfunction. IRAK-M deletion aggravated acute inflammatory response, macrophage activation, and mitochondrial dysfunction following myocardial infarction, with S100A8/A9 acting as a central molecule.
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