FOXO3a Induces Myocardial Fibrosis by Upregulating Mitophagy

Area of Science:

• Cardiology
• Cell Biology
• Molecular Biology

Background:

• Atrial fibrillation is a common arrhythmia linked to myocardial fibrosis and atrial remodeling.
• Myocardial fibrosis contributes to the increased risk of atrial fibrillation.
• The role of forkhead box protein O3 (FOXO3a) in regulating myocardial fibrosis via mitophagy is investigated.

Purpose of the Study:

• To explore the impact of FOXO3a on myocardial fibrosis.
• To determine if FOXO3a regulates mitophagy in cardiac fibroblasts.
• To elucidate the molecular mechanisms linking FOXO3a, fibrosis, and mitophagy.

Main Methods:

• Assessed cell viability (CCK-8), proliferation (EDU), migration (wound healing), and reactive oxygen species.
• Analyzed protein and mRNA expression (Western blotting, qRT-PCR) of key fibrotic and mitophagy markers (e.g., Collagen I, LC3, PINK1, Parkin).
• Utilized immunofluorescence and JC-1 staining to evaluate protein localization and mitochondrial membrane potential.

Main Results:

• Angiotensin II (AngII) upregulated FOXO3a and promoted cardiac fibroblast activation, proliferation, migration, and collagen secretion.
• FOXO3a knockdown significantly inhibited AngII-induced fibroblast activation and fibrosis markers.
• AngII treatment increased mitophagy markers (LC3 II/I, PINK1, Parkin) and decreased p62, effects attenuated by FOXO3a knockdown.

Conclusions:

• FOXO3a promotes myocardial fibrosis progression by inducing mitophagy in cardiac fibroblasts.
• FOXO3a plays a critical role in cardiac fibroblast activation and extracellular matrix remodeling.
• Targeting FOXO3a-mediated mitophagy may offer a novel therapeutic strategy for atrial fibrillation.