Very recently, we have demonstrated that pretreatment of irisin protected the heart against ischemia/reperfusion injury and attenuated the susceptibility of cardiomyoblasts exposed to hypoxic stress, which is closely related to the improvement in mitochondria respiration, reduction of mitochondria apoptosis, inhibition of histone deacetylase 4 (HDAC4) (Zhang et al., 2014; Zhao et al., 2016; Wang et al., 2017). Here, HDAC4 is linked to ischemia.