title: Improvement of cardiac function in the failing rat heart after transfer of skeletal myoblasts engineered to overexpress placental growth factor.
abstract: BACKGROUND
  Transplant of skeletal myoblasts is an attractive alternative to repair irreversibly damaged myocardium in ischemic heart failure. We investigated whether transplant of myoblasts overexpressing placental growth factor would stimulate angiogenesis and enhance myoblast survival in a rat heart failure model.
  
  
  METHODS
  Three weeks after myocardial infarction, Sprague-Dawley rats in heart failure received intramyocardial injections of Ringer solution (control) or autologous myoblasts, unmodified or transfected with placental growth factor expression plasmid. Sham-operated animals served as noninfarct controls. Cardiac function was assessed by echocardiography to 86 days after engraftment. Immunocytochemistry and fluorescence imaging were used to investigate vessel formation, grafted myoblast survival, infarct wall thickness, and infarct size. Quantitative real-time reverse transcriptase polymerase chain reaction and Western blotting measured tissue messenger RNA and protein expressions.
  
  
  RESULTS
  Left ventricular function significantly improved with time, and fractional shortening on day 86 was significantly enhanced in transfected myoblast group relative to control (P < .01) and unmodified myoblast (P < .05) groups. Vascular density (P < .01) and myoblast survival (P < .05) were enhanced in rats treated with transfected myoblasts relative to other groups (P < .05). Mean fraction of fibrotic scar tissue was decreased in unmodified and transfected myoblast groups relative to controls on day 86 (P < .05), and left ventricular wall thickness was significantly increased in transfected myoblast group relative to other groups (P < .05).
  
  
  CONCLUSIONS
  Intramyocardial injections of autologous myoblasts overexpressing placental growth factor improved cardiac function, attenuated adverse cardiac remodeling, induced angiogenesis, and probably enhanced survival of grafted myoblasts.
authors.affiliation: Laboratory for Cardiovascular Research, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gmeiner
authors.forename: Daniel
authors.initials: D
authors.lastname: Zimpfer
authors.forename: Johannes
authors.initials: J
authors.lastname: Holfeld
authors.forename: Gernot
authors.initials: G
authors.lastname: Seebacher
authors.forename: Dietmar
authors.initials: D
authors.lastname: Abraham
authors.forename: Michael
authors.initials: M
authors.lastname: Grimm
authors.forename: Seyedhossein
authors.initials: S
authors.lastname: Aharinejad
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D004195:Disease Models, Animal; D005355:Fibrosis; D015316:Genetic Therapy; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014182:Transplantation, Autologous; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D000072483:Placenta Growth Factor; D020782:Matrix Metalloproteinases