Neuregulin-1β for the treatment of systolic heart failure

The Neuregulin-1 gene encodes a family of ligands that act through the ErbB family of receptor tyrosine kinases to regulate morphogenesis of many tissues. Work in isolated cardiac cells as well as genetically altered mice demonstrates that neuregulin-1/ErbB signaling is a paracrine signaling system that functions in endocardial-endothelial/cardiomyocyte interactions to regulate tissue organization during development as well as maintain cardiac function throughout life. Treatment of animals with cardiac dysfunction with recombinant neuregulin-1beta improves cardiac function. This has led to ongoing early phase clinical studies examining neuregulin-1beta as a potential novel therapeutic for heart failure. In this review we synthesize the literature behind this rapidly evolving area of translational research. This article is part of a special issue entitled “Key Signaling Molecules in Hypertrophy and Heart Failure.”

► Neuregulin-1β(Nrg-1β) is a growth and survival factor in the heart and other organs. ► Nrg-1β works in cardiac myocytes via erbB2 and erbB4 receptor tyrosine kinases. ► Nrg-1β/erbB signaling in the heart regulates myocardial adaptation to stress. ► Recombinant Nrg-1β improves heart function in animal models of heart failure (HF). ► Recombinant human Nrg-1β is now being tested in humans as a possible HF therapy.