Therefore, although modulation of cardiomyocyte stress-signaling by endothelial GADLORs is desirable to a certain extent, aggravated GADLOR abundance clearly triggers heart failure, which is at least in part the consequence of reduced p38 and Akt as well as enhanced calcineurin activation; cardiomyocyte-specific genetic depletion of p38 or general depletion of Akt1 in mice induced aggravated cardiac dysfunction after TAC [37,38]. This evidence concerns the gene AKT1 and persistent truncus arteriosus.