Neuregulin-1/erbB activities with focus on the susceptibility of the heart to anthracyclines

Table 1 Biological effects of neuregulin-1/erbB in embryonic and postnatal cardiomyocytes

Experimental system	Monitored response	Intracellular signal	Ref.
Cultured cells
NRG1 administration in neonatal cardiomyocytes	Sarcomeric F-actin polymerization	PI 3’-kinase	[16]
	Myofibrillogenesis - Growth	Ras-Mek-erk1/2	[17]
	Proliferation	PI 3’-kinase	[17]
	NOS activation		[42]
	Muscarinic activation		[43]
	Karyo- cytokinesis		[44]
NRG1 administration in human ESC	Specification of cardiomyocytes of the conduction lineage		[45]
Animal models
NRG1b injection to ex vivo developing E12.5 dpc mouse	Differentiation of trabeculae		[17]
	DNA synthesis, Proliferation	PI 3’-kinase	[17]
NRG1 administration in mouse with heart failure	Improved cardiac performance		[40]
Hypomorphic NRG1 deficiency in E8.5dpc mouse	Destabilization of gene regulatory network in the left ventricle	Erk1/2	[39]
Mouse ventricular-erbB2-KO	Overt dilation and reduced survival in erbb2 F/- postnatal mouse		[31]
Mouse ventricular-erbB2-KO	Dilation with cellular apoptosis		[32]
Mouse ventricular-erbB4-KO	Overt ventricular dilation at 3 mo and reduced survival		[33]
Lapatinib inhibition of erbB1/erbB2 in Mouse	erbB2-physiologic hypertrophy in pregnancy	MEK1/erk1/2	[34]
Adult ventricular-erbB4-KO	Cell division in myocardial infarction		[44]

Summary of cardiac activities of neuregulin-1 (NRG1)-erbB2/erbB4 signaling inferred from in vitro system and animal model studies. The NRG1 activities, -proliferation, myofibrillogenesis, ventricular remodeling, and repair-, were assessed based on the outcomes of the exogenous administration of NRG1 or by the complete or partial loss of erbB2/erbB4 signaling. NOS: Nitric oxide synthase; MEK1: Mitogen activated kinase erk kinase 1; ESC: Embryonic stem cells.