title: Human hepatocyte growth factor (VM202) gene therapy via transendocardial injection in a pig model of chronic myocardial ischemia.
abstract: BACKGROUND
  Hepatocyte growth factor (HGF) may stimulate angiogenesis. We examined the safety and therapeutic potential of the HGF plasmid (VM202) in pigs with chronic myocardial ischemia.
  
  
  RESULTS
  We delivered VM202 or vehicle transendocardially to 4 groups of pigs: vehicle control (n = 9); high-dose VM202 (n = 9); low-dose VM202 (n = 3); and normal control (no ischemia; n = 1). Pigs were killed 3, 30, and 60 days after injection. No adverse events were associated with VM202 treatment or delivery. Quantitative polymerase chain reaction indicated that heart injection sites had the highest levels of VM202 (day 3), which became almost undetectable by 30-60 days. Most nontarget tissues showed clearance of VM202 plasmid by day 30. Control and VM202-treated pigs did not differ in global functional data. Dobutamine-stressed myocardial-contrast echocardiogram suggested that VM202 may help preserve microvascular perfusion at 30 days; reperfusion velocity in ischemic myocardium decreased significantly in control (baseline to follow-up, 5.1 ± 1.9 to 2.7 ± 1.0; P = .031) but not in VM202 groups (high-dose: 3.1 ± 1.1 vs 3.1 ± 1.5 [P = .511]; low-dose: 3.8 ± 1.1 vs 3.9 ± 1.5 [P = .559]). Linear local shortening increased significantly from day 0 to 30 in VM202-treated versus control pigs (5.0 ± 4.7% vs 9.2 ± 7.5% vs 0.9 ± 5.8% [high-dose, low-dose, control, respectively]; P = .021).
  
  
  CONCLUSIONS
  Transendocardial delivery of VM202 was safe and may help to preserve microcirculatory perfusion and improve wall motion.
authors.affiliation: Stem Cell Center, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas, USA. eperin@bluegate.com
authors.forename: Emerson C
authors.initials: EC
authors.lastname: Perin
authors.forename: Guilherme V
authors.initials: GV
authors.lastname: Silva
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Vela
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Fred
authors.initials: F
authors.lastname: Baimbridge
authors.forename: Amir
authors.initials: A
authors.lastname: Gahremanpour
authors.forename: Xin
authors.initials: X
authors.lastname: Quan
authors.forename: Woong
authors.initials: W
authors.lastname: Hahn
authors.forename: Jongmook
authors.initials: J
authors.lastname: Kim
authors.forename: Krissy
authors.initials: K
authors.lastname: Wood
authors.forename: Marina
authors.initials: M
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004699:Endocardium / Q000473:pathology / Q000502:physiology; D005112:Extracorporeal Circulation / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage* / Q000235:genetics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D034421:Sus scrofa; D013552:Swine
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor