Treatment of dilated cardiomyopathy with electroporation of hepatocyte growth factor gene into skeletal muscle.
Hepatocyte growth factor (HGF) is a potent angiogenic and antifibrotic factor. Cardioprotective effects of HGF for idiopathic dilated cardiomyopathy were examined in hamsters with electroporation of plasmid DNA into skeletal muscle. We used hamster skeletal muscle as a protein producer of HGF gene. A plasmid vector encoding HGF (HGF group, n=12) or empty plasmid (placebo group, n=12) was transferred with in vivo electroporation into tibialis anterior muscles of hamsters with inherited dilated cardiomyopathy (TO-2 strain). The HGF group had greater serum HGF levels (21.6+/-2.2 versus 0.11+/-0.07 ng/mL, P<0.05), higher left ventricular ejection fraction (47.9+/-9.4% versus 28.8+/-11.2%, P<0.05), and greater wall thickening (31.6+/-6.3% versus 19.7+/-6.1%, P<0.05) when compared with the placebo group. The HGF group had smaller areas of ventricular fibrosis (11.8+/-3.4% versus 17.1+/-3.5%, P<0.05) and lower hydroxyproline content (3.7+/-0.7 versus 5.1+/-0.9 micromol/g, P<0.05) than did the placebo group. The HGF group also had higher capillary density (1885+/-232 versus 1447+/-182 vessel/mm(2), P<0.05) and higher matrix metalloprotease-1 activity (13.1+/-3.5 versus 8.1+/-3.6 microg/collagen degraded per hour per gram tissue, P<0.05) than did the placebo group. Exogenous HGF might improve the deleterious changes in myocardial function and structure in the hamster with dilated cardiomyopathy. Systemic delivery of gene products with in vivo electroporation into skeletal muscle seemed to be an alternative means of direct gene delivery.
Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan kkoma@hsp.ncvc.go.jp
Kazuo
K
Komamura
Rie
R
Tatsumi
Jun-ichi
J
Miyazaki
Kunio
K
Matsumoto
Eiji
E
Yamato
Toshikazu
T
Nakamura
Yoshito
Y
Shimizu
Takeshi
T
Nakatani
Soichiro
S
Kitamura
Hitonobu
H
Tomoike
Masafumi
M
Kitakaze
Kenji
K
Kangawa
Kunio
K
Miyatake
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006224:Cricetinae; D018274:Electroporation; D005355:Fibrosis; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000627:therapeutic use; D006352:Heart Ventricles / Q000737:chemistry / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000235:genetics* / Q000502:physiology; D006909:Hydroxyproline / Q000032:analysis; D008297:Male; D008647:Mesocricetus; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000473:pathology; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000503:physiopathology
D017228:Hepatocyte Growth Factor; D006909:Hydroxyproline