title: Comparison of protein with DNA therapy for chronic myocardial ischemia using fibroblast growth factor-2.
abstract: OBJECTIVE
  Treatment of coronary disease by growth factors has become an increasingly used strategy for otherwise untreatable patients and is subject to a number of clinical studies. The aim is to stimulate the development of a sufficient collateral circulation and hereby to rescue cardiac function. The objective of our study was to compare the effectiveness of fibroblast growth factor-2 (FGF-2) as protein and as naked plasmid DNA in a porcine model of chronic myocardial ischemia.
  
  
  METHODS
  A severe stenosis of the left anterior descending artery (LAD) artery was created in healthy pigs. After 1 week, perfusion and regional and global contractility was assessed at baseline at rest and under stress. Afterwards, recombinant FGF-2 (n=6) or naked plasmid DNA encoding FGF-2 (n=7) was intramyocardially injected into the LAD territory. Control animals were left untreated (n=5). After 3 months, the animals were re-examined and underwent immunohistologic analysis. One animal received an Enhanced Green Fluorescent Protein plasmid.
  
  
  RESULTS
  Plasmid-dependent protein synthesis was present in cardiomyocytes. FGF-2 protein as well as plasmid injections resulted in an increased number of capillaries and of arterioles compared with untreated ischemia. The improvement of the regional myocardial blood flow by FGF-2 plasmid therapy at rest might however indicate the effectiveness of the DNA application for the induction of a collateral circulation. A benefit from FGF-2 plasmid therapy was revealed with regard to regional contractility. Systemic hemodynamics were partially improved following plasFGF-2 treatment.
  
  
  CONCLUSIONS
  In this porcine model of chronic myocardial ischemia, intramyocardial injection of FGF-2 plasmid was more effective than of FGF-2 protein in improving regional perfusion and contractility compared to untreated ischemia.
authors.affiliation: Department of Cardiovascular Surgery, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Heilmann
authors.forename: Patrick
authors.initials: P
authors.lastname: von Samson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schlegel
authors.forename: Tim
authors.initials: T
authors.lastname: Attmann
authors.forename: Bernd Ulrich
authors.initials: BU
authors.lastname: von Specht
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Beyersdorf
authors.forename: Georg
authors.initials: G
authors.lastname: Lutter
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2