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

Area of Science:

• Cardiovascular Research
• Neuroscience
• Immunology

Background:

• Myocardial infarction (MI) causes cardiac issues, immune responses, and nervous system activation.
• Neural and neuroimmune mechanisms post-MI are not well understood.

Purpose of the Study:

• To investigate the neural and neuroimmune pathways involved in post-MI cardiac complications.
• To identify potential therapeutic targets for mitigating MI pathology.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) and single-nuclei RNA-seq (snRNA-seq).
• Tissue clearing and spatial transcriptomics.
• Vagal sensory neuron (VSN) ablation and paraventricular nucleus (PVN) neuron inhibition.
• Superior cervical ganglia (SCG) IL-1β signaling blockade.

Main Results:

• Identified TRPV1-expressing VSNs that increase ventricular innervation post-MI.
• VSN ablation reduced infarct size, cardiac dysfunction, and inflammation.
• MI activated AT1aR neurons in the PVN; their inhibition mimicked VSN ablation benefits.
• SCG showed increased sympathetic innervation and IL-1β signaling post-MI; IL-1β blockade reduced complications.

Conclusions:

• A triple-node heart-brain loop involving VSNs, PVN, and SCG contributes to post-MI pathology.
• Targeting TRPV1 VSNs, PVN neurons, or SCG IL-1β signaling offers potential therapeutic strategies for MI.