Moreover, shift work as induced by reversing the photoperiod twice per week for 12 weeks also significantly promoted MI reperfusion injury (60-minute occlusion of LAD) in sheep.134 Mechanistically, decreased RNA and protein levels of NR1D1 (ie, REV-ERBα) were observed in human, mouse, and sheep hearts in MI that occurred after shift work (Figure 2D), while other circadian genes remained unchanged or increased.134 Conditional cardiomyocyte-specific Nr1d1 knockout mice (Myh6CreMer:Nr1d1flox and Nr1d1cKO) showed worsened cardiac damage after MI. This evidence concerns the gene NR1D1 and myocardial infarction.