Likewise, gain and loss of ERK1/2 signaling may explain the beneficial and deleterious effects on myocyte survival and infarct size of exogenous FGF21 and Fgf21 knock-out, respectively, in mice subjected to ischemia–reperfusion injury or permanent coronary artery ligation27,28, although other ERK1/2-independent pathways may also be involved31,33,34. This evidence concerns the gene FGF21 and ischemia.