RESEARCH ARTICLE Recombinant Neuregulin 1 Does Not Activate Cardiomyocyte DNA Synthesis in Normal or Infarcted Adult Mice

Objectives: Neuregulin 1 signaling plays an important role in cardiac trabecular development, and in sustaining functional integrity in adult hearts. Treatment with neuregulin 1 enhances adult cardiomyocyte differentiation, survival and/or function in vitro and in vivo. It has also been suggested that recombinant neuregulin 1b1 (NRG1b1) induces cardiomyocyte proliferation in normal and injured adult hearts. Here we further explore the impact of neuregulin 1 signaling on adult cardiomyocyte cell cycle activity. Methods and Results: Adult mice were subjected to 9 consecutive daily injections of recombinant NRG1b1 or vehicle, and cardiomyocyte DNA synthesis was quantitated via bromodeoxyuridine (BrdU) incorporation, which was delivered using mini-osmotic pumps over the entire duration of NRG1b1 treatment. NRG1b1 treatment inhibited baseline rates of cardiomyocyte DNA synthesis in normal mice (cardiomyocyte labelling index: 0.019¡0.005 % vs. 0.003¡0.001%, saline vs. NRG1b1, P,0.05). Acute NRG1b1 treatment did result in activation of Erk1/2 an