POLE3 and heart failure: Heatmap presentations showed that NME1, POLE3, POLD2, ENTPD6, PNP genes from pyrimidine, purine metabolism signaling pathway and LDHA, AHCY, AMD1 genes from cysteine, methionine metabolism signaling pathway were all down regulated in failing heart tissues in GSE5406, GSE16499 and GSE68316 datasets (Fig. 3b), suggesting the suppression of those pathways in the development of heart failure.