Similarly, using TAC to provoke cardiac disease-mimetic ER stress, we observe a significant reduction in Pak2 phosphorylation and further upregulation of Nrf2 in the hearts of mice after 5 weeks of pressure overload (Figures 2F,G), showing severe cardiac dysfunction (Supplementary Figure 4C) and CHOP upregulation (Figure 2F). This evidence concerns the gene DDIT3 and heart disorder.