CKAP4 Promotes Atrial Fibrosis and Enhances Atrial Fibrillation Vulnerability via WNT/β-Catenin Activation

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• Atrial fibrillation (AF) is a common arrhythmia linked to atrial fibrosis.
• Cytoskeleton-associated protein 4 (CKAP4) is implicated in fibroblast activation, but its role in AF pathogenesis is unknown.

Purpose of the Study:

• To investigate the role of CKAP4 in atrial remodeling and AF susceptibility.
• To elucidate the underlying molecular mechanisms involving the WNT/β-catenin signaling pathway.

Main Methods:

• Serum CKAP4 levels were measured in AF patients and controls.
• CKAP4 expression was analyzed in human single-cell RNA-seq data and mouse models.
• In vitro and in vivo experiments assessed CKAP4 function in atrial fibroblasts and AF inducibility.
• Interactions with WNT3A/WNT5A and β-catenin signaling were examined.

Main Results:

• Serum CKAP4 was elevated in AF patients and correlated with atrial scar burden.
• CKAP4 was enriched in fibroblasts and upregulated in AF.
• CKAP4 knockdown reduced atrial fibrosis and AF inducibility in mice.
• CKAP4 activated WNT/β-catenin signaling in atrial fibroblasts.

Conclusions:

• CKAP4 promotes atrial fibrosis and AF vulnerability via the WNT/β-catenin pathway.
• The CKAP4-WNT/β-catenin axis represents a potential therapeutic target for AF.