Neuregulin signaling and heart failure.

Neuregulin-1 (NRG-1), a ligand of receptor tyrosine kinases of the ErbB family, plays a critical role in cardiovascular development and maintenance of adult heart function. Results from cellular, animal, and clinical experiments have shown NRG-1 to be a promising drug candidate for restoring cardiac function after cardiac injury. Various mechanisms have been suggested to be involved in this process, such as improving sarcomeric structure or cell-cell adhesion, promoting proliferation and survival of cardiac myocytes, balancing Ca(2+) homeostasis, modulating inotropic effects, promoting angiogenesis, and preventing atherosclerosis. However, the contribution of these effects to the restoration of cardiac function remains to be estimated, and it may depend on the specific events that led to heart failure. Meanwhile, distinct and crossed signaling pathways downstream of NRG-1 may play a role in these underlying mechanisms, resulting in a complicated network of signaling mediating the function of NRG-1.