Integrated Metabolomics and Proteomics Analysis of the Myocardium in a Mouse Model of Acute Viral Myocarditis

Abstract

Background

Acute viral myocarditis (AVMC) is a common inflammatory disease affecting the myocardium and is often accompanied by severe metabolic disturbances. The molecular mechanisms underlying this disease are complex and not yet fully understood.

Methods and Results

Coxsackievirus B3 (CVB3)-induced AVMC mouse models were established. By integrating ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based metabolomics and data-independent acquisition (DIA)-based proteomics, we aimed to investigate the global influence of CVB3 infection on the myocardial metabolome and proteome in mice. Based on the criterion of OPLS-DA VIP > 1.0 and p value < 0.05, a total of 149 differential metabolites (DMs) were identified, including 64 upregulated and 85 downregulated metabolites. Bioinformatics analysis revealed that these DMs were mostly enriched in Global and overview maps (Metabolic pathways), Energy metabolism (Sulfur metabolism and Nitrogen metabolism), Amino acid metabolism (Taurine and hypotaurine metabolism, Lysine degradation, and Arginine and proline metabolism), and Carbohydrate metabolism (Propanoate metabolism). Differential analysis also identified 1385 differential proteins (DPs) between the two groups (|Fold Change| >1.5 and p value < 0.05), including 1092 upregulated and 293 downregulated proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DPs indicated that metabolism-related pathways were significant components of the AVMC process. Next, we mined many DPs engaged in the above metabolic pathways through an integrated analysis of KEGG pathway-based metabolomics and proteomics data.

Conclusions

Our integrated metabolomics and proteomics analysis revealed characteristic alterations in metabolites and proteins in the myocardium of AVMC, as well as the associations between them. This not only extends the existing understanding of the molecular basis of the pathogenesis and progression of AVMC but also suggests new directions for its treatment.