IFI-16 inhibition attenuates myocardial remodeling following myocardial infarction

Area of Science:

• Cardiology
• Immunology
• Molecular Biology

Background:

• Myocardial remodeling (MR) post-myocardial infarction (MI) is a major cause of heart failure.
• Inflammation significantly influences cardiac remodeling, making inflammatory factors potential therapeutic targets.
• The role of pattern recognition receptors, like interferon gamma-inducible protein-16 (IFI-16), in post-MI inflammation is not fully understood.

Purpose of the Study:

• To investigate the role of IFI-16 in initiating inflammasome-mediated inflammation post-MI.
• To explore the direct interaction between IFI-16 and galectin-3.
• To evaluate the therapeutic potential of inhibiting IFI-16 in mitigating cardiac remodeling.

Main Methods:

• Quantification of IFI-16 levels in human and rat myocytes and a mouse MI model.
• Genetic suppression of IFI-16 using shRNA lentivirus and adeno-associated virus.
• Assessment of inflammatory markers, cardiac remodeling, and cardiac function.
• Co-immunoprecipitation and double-fluorescence staining to confirm protein interactions.

Main Results:

• Elevated IFI-16 levels were observed in cardiac cells and post-MI hearts, correlating with inflammation.
• Suppression of IFI-16 reduced inflammatory factor activation, mitigated cardiac remodeling, and improved cardiac function.
• Direct interaction between IFI-16 and galectin-3 was confirmed.

Conclusions:

• IFI-16 acts as a critical pro-inflammatory factor in myocardial remodeling following MI.
• IFI-16's interaction with galectin-3 is a key mechanism in this process.
• Inhibition of IFI-16 presents a promising therapeutic strategy for heart failure post-MI.