The Heart's Hidden Neural Network: Interplay Between Intracardiac Ganglia, Fibrosis and Cardiac Remodeling

Area of Science:

• Cardiology
• Neuroscience
• Fibrosis Research

Background:

• The heart's function depends on its intrinsic cardiac nervous system (ICNS), a network integrating local signals.
• Cardiac fibrosis and neuronal remodeling are increasingly recognized as interconnected processes.
• Autonomic imbalance and arrhythmias are linked to ICNS dysfunction.

Purpose of the Study:

• To review the molecular, structural, and functional remodeling of the ICNS.
• To explore how ICNS remodeling drives neurofibrosis, autonomic imbalance, and arrhythmogenesis.
• To integrate knowledge on ICNS, fibrosis, and cardiac electrical instability.

Main Methods:

• Literature synthesis of current knowledge on ICNS anatomy, neurochemistry, and fibrotic mechanisms.
• Mapping fibrotic pathways onto intracardiac ganglia.
• Integrating functional data linking ICNS changes to autonomic dysregulation and arrhythmias.

Main Results:

• Shared pathways (e.g., IL-6/STAT3, TGF-β/SMAD) are implicated in neurofibrotic remodeling across various cardiac conditions.
• ICNS remodeling suppresses neuronal excitability and promotes neuron-glia-fibroblast coupling.
• Neurofibrosis is identified as a key contributor to autonomic dysregulation and arrhythmia vulnerability.

Conclusions:

• The ICNS is a dynamic hub involved in cardiac fibrosis and electrical instability.
• Recognizing neurofibrosis as a companion to myocardial fibrosis reframes therapeutic strategies.
• Future research should focus on human ICNS atlases and multi-omics to guide targeted interventions.