Exercise Training Alleviates Cardiac Fibrosis through Increasing Fibroblast Growth Factor 21 and Regulating...

Area of Science:

• Cardiovascular research
• Exercise physiology
• Molecular cardiology

Background:

• Myocardial infarction (MI) often leads to cardiac fibrosis and dysfunction.
• Exercise training shows promise in mitigating post-MI cardiac damage.
• The precise molecular mechanisms, particularly the role of Fibroblast Growth Factor 21 (FGF21), remain incompletely understood.

Purpose of the Study:

• To investigate if exercise training upregulates FGF21 protein expression post-MI.
• To determine if exercise modulates the transforming growth factor-β1 (TGF-β1)-Smad2/3-MMP2/9 pathway.
• To elucidate the role of FGF21 in exercise-induced cardioprotection against cardiac fibrosis.

Main Methods:

• Established myocardial infarction (MI) model in wild-type and Fgf21 knockout mice.
• Subjected mice to 5 weeks of aerobic exercise training (AET) or resistance exercise training (RET).
• Utilized in vitro studies with cardiac fibroblasts (CFs) exposed to H2O2, treated with recombinant human FGF21 (rhFGF21) and/or AICAR.

Main Results:

• Both AET and RET improved cardiac function, reduced fibrosis, increased FGF21, and inhibited the TGF-β1-Smad2/3-MMP2/9 pathway.
• FGF21 knockout mice exhibited diminished cardioprotective effects from AET post-MI.
• In vitro, rhFGF21 and AICAR suppressed TGF-β1-Smad2/3-MMP2/9 activation, reduced collagen, and promoted CF apoptosis.

Conclusions:

• Exercise training enhances FGF21 expression, which is critical for alleviating cardiac fibrosis post-MI.
• Exercise inactivates the TGF-β1-Smad2/3-MMP2/9 pathway, reducing fibrosis, oxidative stress, and apoptosis, thereby improving cardiac function.
• FGF21 plays a significant role in the anti-fibrotic benefits of exercise training following myocardial infarction.