title: Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.
abstract: OBJECTIVE
  We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease.
  
  
  BACKGROUND
  Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy.
  
  
  METHODS
  rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated.
  
  
  RESULTS
  Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure.
  
  
  CONCLUSIONS
  These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.
authors.affiliation: Zensun Sci & Tech Ltd., Shanghai, China.
authors.forename: Xifu
authors.initials: X
authors.lastname: Liu
authors.forename: Xinhua
authors.initials: X
authors.lastname: Gu
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Li
authors.forename: Xinyan
authors.initials: X
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Jianjie
authors.initials: J
authors.lastname: Chang
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Bing
authors.initials: B
authors.lastname: Xi
authors.forename: Denghong
authors.initials: D
authors.lastname: Chen
authors.forename: Donna
authors.initials: D
authors.lastname: Lai
authors.forename: Robert M
authors.initials: RM
authors.lastname: Graham
authors.forename: Mingdong
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy* / Q000821:virology; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D004317:Doxorubicin; D004452:Echocardiography; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000150:complications*; D009205:Myocarditis / Q000150:complications; D020890:Neuregulin-1 / Q000502:physiology*; D010446:Peptide Fragments; D051381:Rats; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D011994:Recombinant Proteins; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
chemical_list: D004317:Doxorubicin; D020890:Neuregulin-1; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins