ZBED6 deficiency drives pathological cardiac hypertrophy through MEOX1-ERK1/2-dependent autophagy dysfunction.

ZBED6 deficiency is linked to pathological cardiac hypertrophy through activation of the MEOX1-ERK1/2 pathway, impairing autophagy in cardiomyocytes.

• Why it matters: Understanding the molecular mechanisms underlying cardiac hypertrophy is crucial for developing targeted therapies, as current treatments are limited and hypertrophy is a major risk factor for heart failure.
• What they did: The study used transcriptomic and ChIP-seq analyses in human tissues and pig models, revealing that ZBED6 suppression increases MEOX1 expression, which activates ERK1/2 signaling and disrupts autophagy.
• The result: Inhibiting ERK1/2 or knocking down MEOX1 reduced hypertrophy and restored autophagy, suggesting the ZBED6-MEOX1-ERK1/2 axis as a potential therapeutic target for cardiac hypertrophy.