Enhancement of calcium uptake via the sarcoplasmic reticulum is a potent therapeutic strategy for dilated cardiomyopathy and heart failure

Dilated cardiomyopathy (DCM), a distinct form of cardiomyopathy, is a myoca rdial disorder characterised by heart chamber dilation with severe contract ile dysfunction and frequent association with heart failure. Analysing this subset of heart failure has provided mechanistic insights of intrinsic pat hways for myocyte adaptation and survival. Despite the heterogeneous aetiol ogies, a calcium cycling defect is common in DCM. A growing body of evidenc e has shown that calcium homeostasis and calcium-dependent signalling pathw ays play a pivotal role in cardiac hypertrophy and heart failure. In this r egard, recent studies demonstrate that a cardiac calcium cycling defect is identified as a critical regulator for the progression of heart failure in DCM and that enhancement of calcium uptake into the cardiac sarcoplasmic re ticulum (SR) may have potential therapeutic value for cardiac dysfunction. This article will focus on the cardiac SR calcium ATPase (SERCA2a) and its regulatory protein, phospholamban (PLB), as new therapeutic targets for DCM and heart failure.