Macrophage PARP7 Alleviates Septic Cardiomyopathy by Interacting With TBK1 and Suppressing TBK1-Driven Inflammatory Response.

Summary

This study identifies a macrophage-specific PARP7-TBK1 regulatory axis that limits excessive inflammation in septic cardiomyopathy. PARP7 deficiency worsened cardiac injury, whereas AAV9-mediated macrophage-specific PARP7 expression was cardioprotective in both lipopolysaccharide and cecal ligation and puncture mouse models.

Key Findings

• PARP7 deficiency exacerbated lipopolysaccharide-induced septic cardiomyopathy in vivo.
• Single-nucleus and single-cell RNA sequencing localized the major PARP7 response to cardiac macrophages.
• Macrophage-specific PARP7 interacted with TBK1 through ADP-ribosylation and reduced TBK1-driven inflammation in lipopolysaccharide and cecal ligation and puncture models.

Clinical Implications

Macrophage PARP7 enhancement could become a future strategy for preventing or treating septic cardiac dysfunction, but delivery specificity, immunogenicity, dosing, and effects on pathogen control must be established before clinical translation.

Limitations

• The evidence is preclinical and based on murine lipopolysaccharide and cecal ligation and puncture models.
• The provided abstract does not report animal numbers, long-term outcomes, pathogen-specific effects, or the safety profile of AAV9-mediated PARP7 overexpression.

Future Directions

Future studies should assess PARP7 modulation in polymicrobial infections with contemporary clinical care, define the therapeutic window and optimal delivery platform, and evaluate whether targeted PARP7 enhancement improves survival without impairing antimicrobial immunity.