In an acute myocardial infarction mice model, it was revealed that supplementation of IL-22 markedly prevented left ventricular dysfunction and heart failure via liver-derived STAT3-FGF21 production, in which hepatocyte-specific knockout of STAT3 or FGF21 blocked such alleviation of IL-22 121. Here, STAT3 is linked to acute myocardial infarction.