We demonstrated, for the first time, that SPC administration increased RIPK3 protein O-GlcNAc levels in an OGT dependent manner and that augmentation of this response was associated with reduced myocardial infarction size, restoration of cardiac function, and decreased necroptosis following simulated ischemia reperfusion injury in vivo and in vitro. Here, RIPK3 is linked to myocardial infarction.