title: Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte growth factor from naked plasmid DNA in a rat ischemic heart disease model.
abstract: BACKGROUND
  The therapeutic potential of pCK-HGF-X7, a naked DNA designed to express two isoforms of hepatocyte growth factor (HGF(723) and HGF(728) ), was studied in the rat ischemic heart disease model.
  
  
  METHODS
  First, the kinetics of gene expression was examined by injecting pCK-HGF-X7 DNA into the rat heart. Second, the cardioprotective effects were compared between the two naked DNA constructs, expressing a single (HGF(728) ) or both isoforms (HGF(728) and HGF(723) ) of HGF, in the rat ischemic heart disease model. The ischemic injury to the rat heart was created by ischemia-reperfusion in the anterior descending artery. The respective naked DNA constructs were injected into the anterior wall of the rat heart with the ischemia-reperfusion injury. Cardiac function, capillary density and anti-fibrotic activity were compared between the two naked DNA constructs.
  
  
  RESULTS
  The intramyocardial administration of pCK-HGF-X7 resulted in transient and localized HGF expression for 3 weeks. At its peak, approximately 678 pg (per mg of tissue protein) of HGF was produced in the injected heart without an increase of HGF protein level in other tissues, and serum. pCK-HGF-X7 more efficiently improved the left ventricular ejection fraction and the systolic anterior wall thickness, increased the capillary density, and inhibited myocardial fibrosis, in a statistically significant manner, compared to the identical vector encoding HGF(728) only.
  
  
  CONCLUSIONS
  These results demonstrate that transfer of the genomic-cDNA hybrid expressing both isoforms of the HGF gene might provide higher therapeutic effects than the cDNA sequence producing HGF(728) alone in the treatment of ischemic heart disease.
authors: ViroMed Co., Ltd, Seoul National University, Seoul, Korea.
authors: Woong
authors: W
authors: Hahn
authors: Wook-Bum
authors: WB
authors: Pyun
authors: Dong-Sik
authors: DS
authors: Kim
authors: Won-Sun
authors: WS
authors: Yoo
authors: Sung-Dong
authors: SD
authors: Lee
authors: Jung-Hee
authors: JH
authors: Won
authors: Gil Ja
authors: GJ
authors: Shin
authors: Jong-Mook
authors: JM
authors: Kim
authors: Sunyoung
authors: S
authors: Kim
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology* / Q000628:therapy*; D010957:Plasmids / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020033:Protein Isoforms; D017228:Hepatocyte Growth Factor; D004247:DNA