Molecular Signatures of Sinus Node Dysfunction Induce Structural Remodeling in the Right Atrial Tissue

Area of Science:

• Cardiology
• Molecular Biology
• Pathology

Background:

• Sinus node dysfunction (SND) is linked to cardiovascular issues like heart failure and atrial fibrillation.
• Histological hallmarks of SND include atrial remodeling, conduction abnormalities, and increased right atrial refractoriness.
• The molecular basis of SND-associated right atrial fibrosis remains unclear.

Purpose of the Study:

• To investigate molecular changes in the right atrium (RA) induced by SND.
• To identify molecular mechanisms underlying SND-related structural remodeling of the RA.
• To explore the role of specific factors, like periostin, in SND-induced atrial remodeling.

Main Methods:

• Utilized a rabbit model of experimental SND.
• Compared genome-wide RNA expression profiles in RA between SND-induced and control rabbits.
• Performed gene enrichment analysis to identify differentially expressed transcripts and signaling pathways.

Main Results:

• Identified extensive pro-fibrotic changes in the RA within 7 days of SN ablation.
• Observed activation of transforming growth factor-β (TGF-β) signaling.
• Found alterations in extracellular matrix components and regulators, with periostin identified as a potential key mediator.

Conclusions:

• SND induces significant molecular changes, including pro-fibrotic signaling and extracellular matrix alterations, in the RA.
• Periostin may play a crucial role in mediating TGF-β-induced atrial remodeling.
• Periostin shows potential as a diagnostic marker for fibroproliferative cardiac dysfunctions.