Breakthrough Study Reveals WNT5a-Driven Actin Dysregulation as Core Mechanism in LMNA-Related Cardiac Disease

Highlights

This study uncovers a fundamental molecular mechanism linking LMNA sequence variations to cardiac dysfunction in Emery-Dreifuss muscular dystrophy. The research demonstrates that reduced WNT5a expression leads to RhoA signaling inactivation, causing actin depolymerization and resulting in nuclear envelope deformation, contractile dysfunction, and impaired connexin 43 trafficking. Pharmacological interventions targeting the WNT5a/RhoA/actin pathway effectively rescued pathogenic phenotypes in patient-derived cardiac cells.

Background