Nrf2 + Cluster 1 CF favored ischemia and is characterized by the upregulation of S1PR1 (cardioprotective mediator that acts by maintaining calcium homeostasis) (Keul et al. 2016), AREG (pro-fibrotic mediator) (Liu et al. 2020), and ADAMTS1, the ECM protease that supports remodeling (Wang et al. 2021) with a concomitant downregulation of inflammatory mediators MX2 and CCL5. Here, ADAMTS1 is linked to ischemia.