Abstract 13213: Protective Role of Fgf21 in Adverse Cardiac Remodeling After Myocardial Infarction
Objective: Cardiovascular disease is one of the leading causes of death worldwide. Regular exercise is associated with a cardiovascular risk reduction. Fibroblast growth factor 21 (FGF21) is secreted from skeletal muscle and upregulated by exercise training. Here, we investigated whether skeletal muscle-derived FGF21 affects cardiac remodeling in mice following myocardial infarction.
Methods and Results: C57BL/6J wild-type (WT) mice were subjected to myocardial infarction by permanent ligation of the left anterior descending coronary artery (LAD). Mice were intramuscularly treated with an adenoviral vector encoding FGF21 (Ad-FGF21) or control β-galactosidase (Ad-β-gal) at 3 days before LAD ligation. Intramuscular treatment of WT mice with Ad-FGF21 increased plasma levels of FGF21 compared with Ad-β-gal. At 2 weeks after LAD ligation, Ad-FGF21-treated WT mice exhibited improvement of left ventricular systolic function and chamber size, and reduction of myocyte hypertrophy compared to Ad-β-gal-treated mice. Administration of Ad-FGF21 to WT mice also increased capillary density in the infarct border zone as evaluated by CD31 immunostaining and reduced cardiomyocyte apoptosis in the remote zone as assessed by TUNEL staining. In addition, Ad-FGF21 decreased mRNA levels of pro-inflammatory cytokines and fibrotic mediators in the heart of WT mice after myocardial infarction. Moreover, treatment of WT mice with Ad-FGF21 increased plasma levels of a cardioprotective adipokine adiponectin. Of note, intramuscular injection of Ad-FGF21 failed to improve cardiac function and dilatation in adiponectin-deficient mice after myocardial infarction
Conclusions: These data suggest that muscle-derived FGF21 prevents adverse cardiac remodeling after myocardial infarction by its abilities to modulate myocyte hypertrophy and apoptosis, inflammation and angiogenesis in the heart and that adiponectin plays an important role in the cardioprotective action of FGF21.
Author Disclosures: Y. Joki: None. K. Ohashi: None. D. Yuasa: None. R. Shibata: None. T. Kambara: None. S. Hayakawa: None. M. Hiramatsu-Ito: None. H. Ogawa: None. H. Daida: None. T. Murohara: None. N. Ouchi: None.
- © 2014 by American Heart Association, Inc.