title: Intravenous glial growth factor 2 (GGF2) isoform of neuregulin-1β improves left ventricular function, gene and protein expression in rats after myocardial infarction.
abstract: OBJECTIVE
  Recombinant Neuregulin (NRG)-1β has multiple beneficial effects on cardiac myocytes in culture, and has potential as a clinical therapy for heart failure (HF). A number of factors may influence the effect of NRG-1β on cardiac function via ErbB receptor coupling and expression. We examined the effect of the NRG-1β isoform, glial growth factor 2 (GGF2), in rats with myocardial infarction (MI) and determined the impact of high-fat diet as well as chronicity of disease on GGF2 induced improvement in left ventricular systolic function. Potential mechanisms for GGF2 effects on the remote myocardium were explored using microarray and proteomic analysis.
  
  
  RESULTS
  Rats with MI were randomized to receive vehicle, 0.625 mg/kg, or 3.25 mg/kg GGF2 in the presence and absence of high-fat feeding beginning at day 7 post-MI and continuing for 4 weeks. Residual left ventricular (LV) function was improved in both of the GGF2 treatment groups compared with the vehicle treated MI group at 4 weeks of treatment as assessed by echocardiography. High-fat diet did not prevent the effects of high dose GGF2. In experiments where treatment was delayed until 8 weeks after MI, high but not low dose GGF2 treatment was associated with improved systolic function. mRNA and protein expression analysis of remote left ventricular tissue revealed a number of changes in myocardial gene and protein expression altered by MI that were normalized by GGF2 treatment, many of which are involved in energy production.
  
  
  CONCLUSIONS
  This study demonstrates that in rats with MI induced systolic dysfunction, GGF2 treatment improves cardiac function. There are differences in sensitivity of the myocardium to GGF2 effects when administered early vs. late post-MI that may be important to consider in the development of GGF2 in humans.
authors: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Michael F
authors: MF
authors: Hill
authors: Amish V
authors: AV
authors: Patel
authors: Abigail
authors: A
authors: Murphy
authors: Holly M
authors: HM
authors: Smith
authors: Cristi L
authors: CL
authors: Galindo
authors: Laura
authors: L
authors: Pentassuglia
authors: Xuyang
authors: X
authors: Peng
authors: Carrie G
authors: CG
authors: Lenneman
authors: Oghenerukevwe
authors: O
authors: Odiete
authors: David B
authors: DB
authors: Friedman
authors: Marvin W
authors: MW
authors: Kronenberg
authors: Siyuen
authors: S
authors: Zheng
authors: Zhongming
authors: Z
authors: Zhao
authors: Yanna
authors: Y
authors: Song
authors: Frank E
authors: FE
authors: Harrell
authors: Maya
authors: M
authors: Srinivas
authors: Anindita
authors: A
authors: Ganguly
authors: Jennifer
authors: J
authors: Iaci
authors: Tom J
authors: TJ
authors: Parry
authors: Anthony O
authors: AO
authors: Caggiano
authors: Douglas B
authors: DB
authors: Sawyer
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004562:Electrocardiography; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020890:Neuregulin-1 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D049268:Positron-Emission Tomography; D020033:Protein Isoforms / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D014022:Tissue Survival / Q000187:drug effects; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D020890:Neuregulin-1; D020033:Protein Isoforms; D020543:Proteome; C117467:neuregulin beta; D020794:Receptor Protein-Tyrosine Kinases; D005947:Glucose