title: Therapeutic angiogenesis using naked DNA expressing two isoforms of the hepatocyte growth factor in a porcine acute myocardial infarction model.
abstract: OBJECTIVE
  We evaluated the potency of therapeutic angiogenesis using intramyocardial injection of naked DNA expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in a porcine myocardial infarction model.
  
  
  METHODS
  Four weeks after left anterior descending coronary artery ligation, 14 pigs were allocated to pCK-Null (negative control, n=7) or pCK-HGF-X7 (n=7) treatment groups. Gated myocardial single photon emission computed tomography was performed 4 and 8 weeks following coronary ligation. The effect of pCK-HGF-X7 on capillary density in the gene-injected myocardium was examined by histological analysis using alkaline phosphatase staining.
  
  
  RESULTS
  Segmental myocardial perfusion of the underperfused area (< or =70%) from coronary ligation increased in the pCK-HGF-X7 group (p=0.051), without significant differences in changes over time between the two groups (p=0.54). Systolic wall thickening (p=0.001), left ventricular end-diastolic (p=0.045) and end-systolic volumes (p=0.009), and left ventricular ejection fraction (p=0.041) changed in both groups without significant differences in changes over time between the two groups. The increase in the left stoke volume was higher in the pCK-HGF-X7 group than in the pCK-Null group (p=0.008). Histological analysis showed that capillary density was significantly higher in the pCK-HGF-X7 group than the pCK-Null group (p<0.001).
  
  
  CONCLUSIONS
  Intramyocardial injection of pCK-HGF-X7 induced significant angiogenesis at infarct-border zone, and increased the left ventricular stroke volume probably caused by reverse remodeling process.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Cheju Halla General Hospital, Republic of Korea.
authors.forename: Kwang Ree
authors.initials: KR
authors.lastname: Cho
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Choi
authors.forename: Woong
authors.initials: W
authors.lastname: Hahn
authors.forename: Dong Sik
authors.initials: DS
authors.lastname: Kim
authors.forename: Jin Sik
authors.initials: JS
authors.lastname: Park
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.forename: Ki-Bong
authors.initials: KB
authors.lastname: Kim
mesh_terms: D000818:Animals; D002196:Capillaries / Q000473:pathology; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D010957:Plasmids; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013318:Stroke Volume; D034421:Sus scrofa; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D020033:Protein Isoforms; D017228:Hepatocyte Growth Factor