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

Abstract

Dilated cardiomyopathy (DCM), a distinct form of cardiomyopathy, is a myocardial disorder characterised by heart chamber dilation with severe contractile dysfunction and frequent association with heart failure. Analysing this subset of heart failure has provided mechanistic insights of intrinsic pathways for myocyte adaptation and survival. Despite the heterogeneous aetiologies, a calcium cycling defect is common in DCM. A growing body of evidence has shown that calcium homeostasis and calcium-dependent signalling pathways play a pivotal role in cardiac hypertrophy and heart failure. In this regard, 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 reticulum (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.

• calcium ATPase
• calcium homeostasis
• dilated cardiomyopathy
• heart failure
• phospholamban
• sarcoplasmic reticulum