The reduction of PKG-dependent phosphorylation at the N2B-us region may significantly contribute to the augmented diastolic stiffness observed in failing hearts, as ex vivo incubation with PKG has been shown to rectify the increased Fpassive of skinned cardiomyocytes in human cases, including those with HFpEF and AS, with or without DM [12, 13, 59–61], as well as in animal models of HFpEF, diastolic dysfunction, and cardiac hypertrophy [14, 16, 18, 20, 53]. Here, PRKG1 is linked to cardiac hypertrophy.