A triple-node heart-brain neuroimmune loop underlying myocardial infarction.

Summary

This study identifies a tripartite heart–brain neuroimmune circuit after MI involving TRPV1-expressing vagal sensory neurons, AT1aR-positive PVN neurons, and IL-1β signaling within the superior cervical ganglion. Functional disruption at each node attenuated infarct burden, electrical and functional impairment, sympathetic remodeling, and inflammatory responses, nominating neuromodulation and IL-1β blockade as therapeutic strategies.

Key Findings

• TRPV1-expressing vagal sensory neuron ablation reduced infarct size, ECG abnormalities, cardiac dysfunction, sympathetic innervation, and IL-1β after MI.
• MI activated AT1aR-positive PVN neurons; their inhibition reproduced benefits of TRPV1 VSN ablation.
• Superior cervical ganglion showed enhanced post-MI sympathetic innervation and IL-1β signaling; IL-1β blockade in SCG reduced post-MI complications.
• snRNA-seq and spatial transcriptomics indicated reduced border-zone expansion with VSN ablation.

Clinical Implications

While preclinical, the work nominates testable targets—TRPV1 vagal afferents, PVN AT1aR neurons, and IL-1β signaling in the superior cervical ganglion—for adjunctive therapies to mitigate post-MI remodeling and complications.

Limitations

• Preclinical models; human translational validity and safety of neuromodulation remain untested.
• Specificity and durability of node-targeted interventions over long-term remodeling are unknown.

Future Directions

Translate neuromodulatory and cytokine-blocking strategies to large-animal and early-phase human studies; develop targeted delivery to TRPV1 VSNs, PVN AT1aR neurons, or SCG IL-1β pathways; integrate with guideline-directed MI care.