IRAK-M deletion aggravates acute inflammatory response and mitochondrial respiratory dysfunction following myocardial infarction: A bioinformatics analysis

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.