Inhibition of Satellite Glial Cell Activation in Stellate Ganglia Prevents Ventricular Arrhythmogenesis and Remodeling After Myocardial Infarction.

Summary

Chemogenetic manipulation of stellate ganglion satellite glial cells showed that their activation drives early sympathetic hyperexcitability and ventricular electrophysiological instability after MI, whereas inhibition stabilizes electrophysiology and attenuates neural and structural remodeling. Bulk RNA-seq and pharmacologic blockade implicated P2Y1R/IGFBP2 signaling as a key pathway linking SGCs to sympathetic neurons.

Key Findings

• Stellate ganglion SGC activation correlated with norepinephrine release and induced ventricular electrophysiological instability within 2 hours post-MI.
• Inhibition of SGCs suppressed MI-induced sympathetic hyperexcitability and improved ventricular remodeling and function by day 7.
• P2Y1R/IGFBP2 signaling mediated SGC–sympathetic neuron crosstalk; blocking P2Y1R attenuated the pro-arrhythmic effects.

Clinical Implications

Suggests that targeting stellate ganglion glial signaling (e.g., P2Y1R inhibition) could complement existing post-MI therapies to reduce ventricular arrhythmias and adverse remodeling, and refines the rationale for sympathetic neuromodulation approaches.

Limitations

• Preclinical rat models; absence of human interventional validation.
• Short-term observation windows (early hours to 7 days) may not capture chronic remodeling dynamics.

Future Directions

Translate P2Y1R/IGFBP2-targeted neuromodulation to large-animal models and early-phase human studies; evaluate synergy with existing post-MI therapies and device-based sympathetic modulation.