The epidermal growth factor family member neuregulin 1 (NRG1) is required for cardiac development, and administration of recombinant NRG1 (rNRG1) has been proposed as a strategy to promote cardiac regeneration following heart failure. Now, two new papers provide insight into the mechanisms of action of NRG1 and its potential to be therapeutically exploited. D'Uva et al. focused their studies on the NRG1 co-receptor ERBB2, which they show is necessary for NRG1-induced cardiomyocyte (CM) proliferation in neonatal mice and which becomes limited as CMs cease division 1 week after birth. Induction of a constitutively active ERBB2 (caERBB2) in neonatal, juvenile and adult CMs generated pronounced cardiomegaly, whereas transient caERBB2 induction in juvenile or adult mice stimulated CM proliferation and allowed heart regeneration after ischaemic injury. Polizzotti et al. investigated the potential of rNRG1 to treat paediatric heart failure. Thirty-four days of rNRG1 administration to newborn mice subjected to cryoinjury improved myocardial function and reduced transmural scarring through CM protection and proliferation. Moreover, rNRG1 induced CM proliferation in intact cultured myocardium from infants with heart disease who were less than 6 months old.
D'Uva, G. et al. ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nature Cell Bio. 17, 627–638 (2015)
Polizzotti, B. et al. Neuregulin stimulation of cardiomyocyte regeneration in mice and human myocardium reveals a therapeutic window. Sci. Transl Med. 7, 281ra45 (2015)
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Crunkhorn, S. Stimulating cardiomyocyte regeneration after heart failure. Nat Rev Drug Discov 14, 386 (2015). https://doi.org/10.1038/nrd4654