Ischemic heart disease is one of the leading causes of death.
Fibroblast growth factor 21 (
FGF21) is a circulating factor with an anti-diabetic property. Skeletal muscle is an important source of
FGF21 production. Here, we investigated whether skeletal muscle-derived
FGF21 modulates cardiac remodeling in a murine model of
myocardial infarction.
Myocardial infarction was produced in C57BL/6J wild-type (WT) mice by the permanent
ligation of the left anterior descending coronary artery (LAD). Adenoviral vectors expressing
FGF21 (Ad-FGF21) or control β-
galactosidase were intramuscularly injected into mice at 3 days before permanent LAD
ligation.
Intramuscular injection of Ad-FGF21 increased plasma
FGF21 levels in WT mice compared with control. Treatment of WT mice with Ad-FGF21 led to improvement of
left ventricular systolic dysfunction and dilatation at 2 weeks after LAD
ligation. Ad-FGF21 administration to WT mice also led to enhancement of capillary density in the
infarct border zone, and reduction of myocyte apoptosis in the remote zone, which were accompanied by decreased expression of pro-inflammatory
cytokines. Furthermore, treatment of WT mice with Ad-FGF21 increased plasma levels of
adiponectin, which is a cardioprotective
adipokine. The beneficial effects of Ad-FGF21 on cardiac dysfunction and inflammatory response after
myocardial infarction were diminished in
adiponectin-knockout mice. These data suggest that muscle-derived
FGF21 ameliorates adverse cardiac remodeling after
myocardial infarction, at least in part, through an
adiponectin-dependent mechanism.