A recombinant antibody increases cardiac contractility by mimicking phospholamban phosphorylation

ABSTRACT Many cardiovascular disease states end in progressive heart failure. Changes in intracellular calcium handling, including a reduced activity of the sarcoplasmic reticulum calcium pump (SERCA), contribute to this contractile dysfunction. As the regulatory protein phospholamban can inhibit the calcium pump, we evaluated it as a potential target to improve cardiac function. In this study, we describe a recombinant antibody‐based protein (PLN‐Ab) that binds to the cytoplasmic domain of phospholamban. Fluorescence resonance energy transfer (FRET) studies suggest that PLN‐Ab mimics the effects of phospholamban phosphorylation. PLN‐Ab accelerated the decay of the calcium transient when expressed in neonatal rat and adult mouse ventricular cardiac myocytes. In addition, direct injection of adenovirus encoding PLN‐Ab into the diabetic mouse heart enhanced contractility when measured in vivo by echo cardiography and in ex vivo Langendorff perfused hearts. The PLN‐Ab provides a novel therapeutic approach to improving contractility through in vivo expression of an antibody inside cardiac myocytes.