Targeting Calpain for Heart Failure Therapy: Implications From Multiple Murine Models

Highlights •Calpain is hyperactivated in human failing hearts and rodent heart failure models of different etiologies. •Inhibition of calpain activity with MDL-28170 protects against cardiac dysfunction by preserving JP2 expression and T-tubule ultrastructural integrity in murine models of heart failure. •Overexpression of JP2 delays the onset of early cardiac sudden death and heart failure, induced by calpain overactivation.