Dronedarone Attenuates Ang II-Induced Myocardial Hypertrophy Through Regulating SIRT1/FOXO3/PKIA Axis

Area of Science:

• Cardiology
• Molecular Biology
• Pharmacology

Background:

• Pathological myocardial hypertrophy (MH) impairs heart function.
• Dronedarone shows potential in attenuating cardiac hypertrophy.
• The precise molecular mechanisms of dronedarone in MH remain largely unknown.

Purpose of the Study:

• To elucidate the molecular regulatory mechanism of dronedarone in myocardial hypertrophy.
• To investigate the role of the SIRT1/FOXO3/PKIA axis in dronedarone's effects on MH.

Main Methods:

• Utilized Angiotensin II (Ang II) to induce H9C2 cell hypertrophy and transverse aortic constriction (TAC) surgery for a rat MH model.
• Assessed cell size and gene/protein expression via crystal violet staining, rhodamine phalloidin staining, qRT-PCR, and Western blot.
• Employed JASPAR and luciferase assays to validate the interaction between FOXO3 and the PKIA promoter.

Main Results:

• Dronedarone reversed Ang II-induced cell hypertrophy and restored SIRT1 expression.
• SIRT1 and PKIA overexpression enhanced dronedarone's anti-hypertrophic effects.
• Dronedarone improved cardiac function in TAC-induced MH rats by modulating the SIRT1/FOXO3/PKIA signaling pathway.

Conclusions:

• Dronedarone alleviates myocardial hypertrophy by mediating the SIRT1/FOXO3/PKIA axis.
• Findings provide mechanistic insights into dronedarone's therapeutic potential for MH.