title: Therapeutic effects of neuregulin-1 gene transduction in rats with myocardial infarction.
abstract: OBJECTIVE
  In this study, we investigated whether lentivirus-mediated gene transduction improves the cardiac function in rats with myocardial infarction and the mechanisms involved.
  
  
  RESULTS
  Briefly, lentivirus carrying human neuregulin-1 (hNRG-1) gene was injected into infarcted myocardium of rats. Four weeks later, lentivirus-mediated gene transduction promoted hNRG-1 gene and protein expression. Overexpression of hNRG-1 increased the number of microvessels in the ischemic myocardium and decreased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-stained positive cells. Furthermore, qRT-PCR assay showed that hNRG-1 was capable of increasing the expression of bcl-2 and VEGF-A while decreasing the expression of bax. Western blot analysis suggested that overexpression of hNRG-1 activated the PI3K/Akt pathway and increased the phosphorylation of Akt and eNOS.
  
  
  CONCLUSIONS
  These findings suggest that NRG-1 gene transduction can improve cardiac function by promoting angiogenesis and preventing apoptosis.
authors.affiliation: Hypertensive Research Institute, First Affiliated Hospital, Nanchang University, Nanchang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.forename: Bingong
authors.initials: B
authors.lastname: Li
authors.forename: Zeqi
authors.initials: Z
authors.lastname: Zheng
authors.forename: Menghong
authors.initials: M
authors.lastname: Wang
authors.forename: Jingtian
authors.initials: J
authors.lastname: Peng
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D020287:In Situ Nick-End Labeling; D016086:Lentivirus / Q000235:genetics; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D055806:Microvessels / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013318:Stroke Volume; D013997:Time Factors; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000099273:Neurabins
chemical_list: D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D052250:Nitric Oxide Synthase Type III; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D000099273:Neurabins; C494828:Bax protein, rat; C467498:vascular endothelial growth factor A, rat; C496316:Nos3 protein, rat