Omics-based integrative analysis of sepsis-induced myocardial dysfunction

Area of Science:

• Cardiovascular Biology
• Metabolomics
• Systems Biology

Background:

• Sepsis-induced myocardial dysfunction is a critical complication with high mortality.
• The underlying molecular mechanisms of this condition remain largely unknown.

Purpose of the Study:

• To investigate the mechanisms of sepsis-induced myocardial dysfunction using an integrative multiomics approach.
• To identify key molecular alterations in heart tissue during sepsis.

Main Methods:

• Constructed a mouse model of sepsis-induced myocardial dysfunction.
• Performed untargeted metabolomics, transcriptomics, and proteomics on heart tissues.
• Integrated multiomics data to identify common molecular changes.

Main Results:

• Identified significant alterations in 74 metabolites (positive ion mode) and 70 metabolites (negative ion mode).
• Revealed 4831 differentially expressed genes and 107 significant proteins in heart tissue.
• Found L-glutamate, L-aspartate, and nicotinamide as key altered metabolites involved in specific metabolic pathways.

Conclusions:

• Sepsis-induced myocardial dysfunction in mice is potentially linked to dysregulation in nicotinate and nicotinamide metabolism.
• Alterations in histidine metabolism and nitrogen metabolism may also contribute to the pathogenesis.
• Integrative multiomics provides novel insights into the molecular basis of sepsis-induced heart dysfunction.