Getting pumped about heart failure

Abstract

Heart failure is a clinical syndrome caused by dysregulated calcium handling and abnormal cardiac pumping capacity. Wahlquist et al. (2014) show that upregulation of microRNA-25 impairs calcium handling leading to pump dysfunction and that targeting microRNA-25 using antisense oligonucleotides reverses pump dysfunction and improves survival in mice with heart failure.

Figure 1

Model of dysregulated excitation-contraction coupling in heart failure. Tissue injury in heart failure leads to increased expression levels of micro-RNA-25 (miR-25) in the heart. miR-25 binds to messenger RNA for sarcoendoplasmic reticulum Ca2+-ATPase (SERCA2a), which is responsible for pumping cytoplasmic calcium (Ca2+) into the sarcoplasmic reticulum (SR) during relaxation of the heart. Decreased expression levels of SERCA2a result in impaired uptake of cytoplasmic Ca2+ into sarcoendoplasmic reticulum, which leads to diminished pumping capacity of the heart because there is less Ca+ available for activation of the actin and myosin cross-bridges at the onset of the muscle contraction. Sustained pump dysfunction contributes to the development of the clinical syndrome of heart failure. Blocking miR-25 may represent a novel strategy for improving the pumping capacity of the heart in heart failure.