GDF6 Alleviates Pathological Cardiac Hypertrophy via AMPKα Signaling Pathway

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Cell Signaling

Background:

• Cardiac hypertrophy is a precursor to heart failure, driven by complex signaling pathways.
• The role of Growth Differentiation Factor 6 (GDF6) in cardiac hypertrophy is not well understood.
• Investigating GDF6's mechanisms is crucial for understanding and treating cardiac hypertrophy.

Purpose of the Study:

• To elucidate the role and underlying mechanisms of GDF6 in cardiac hypertrophy.
• To determine if GDF6 acts as a protective factor against cardiac hypertrophy.
• To explore the therapeutic potential of GDF6 in heart failure.

Main Methods:

• Utilized adeno-associated virus serotype 9 for GDF6 overexpression and knockdown in mouse hearts.
• Induced pressure overload-induced cardiac hypertrophy via transverse aortic constriction (TAC) surgery.
• Employed echocardiography, histology, molecular analyses, and in vitro studies with neonatal rat ventricular myocytes (NRVMs) stimulated by phenylephrine (PE).

Main Results:

• GDF6 expression increased under hypertrophic stimuli; knockdown worsened hypertrophy, while overexpression attenuated it.
• GDF6 inhibited pressure overload-induced cardiac hypertrophy, inflammation, and dysfunction in vivo.
• GDF6 protected against PE-induced cardiomyocyte hypertrophy in vitro via the cAMP/Epac1/AMPKα pathway.

Conclusions:

• GDF6 acts as a novel negative regulator of cardiac hypertrophy.
• GDF6 exerts cardioprotective effects by activating the AMPKα pathway through cAMP/Epac1.
• GDF6 supplementation represents a potential therapeutic strategy for heart failure.