DDIT3 and heart failure: Specifically, upregulation of PERK/ATF4 signaling and CHOP has been shown to contribute to cardiomyocyte dysfunction and progressive cardiac muscle loss in murine models of ischemic heart disease and heart failure (18, 22), while pharmacological inhibition or cardiomyocyte-specific deletion of CHOP was shown to prevent pathological cardiac remodeling (23).