Gene transfer of hepatocyte growth factor improves angiogenesis and function of chronic ischemic myocardium in canine heart.
BACKGROUND
Hepatocyte growth factor (HGF) induces angiogenesis in myocardium. In the present study, its effects in chronic ischemic myocardium were tested.


METHODS
Four weeks after left anterior descending coronary artery ligation in canine hearts, HVJ-liposome containing either human HGF gene (160 microg; HGF group, n = 7) or nothing (control group, n = 6) was directly injected into ischemic myocardium. Four weeks after gene transfection, the thickness fraction (TF), an index of regional myocardial contractility (assessed by epicardial pulse-Doppler crystals), the myocardial perfusion flow (assessed by color microspheres), and the capillary density (assessed by immunostaining of vessels) were evaluated in ischemic myocardium.


RESULTS
Thickness fraction (percent of nonischemic myocardium) was significantly improved in the HGF group (80 +/- 15 from 52 +/- 16 of pregene; p < 0.05) whereas it was not changed in the control group (52 +/- 10 from 50 +/- 8 of pregene). The perfusion flow (% of nonischemic myocardium) was significantly improved in the HGF group (98 +/- 17 from 51 +/- 14 of pregene; p < 0.05) while it was not changed in the Control group (58 +/- 13 from 62 +/- 18 of pregene). The capillary density was significantly higher in the HGF group (894 +/- 211/mm2; p < 0.05) than that in the control group (511 +/- 127/mm2).


CONCLUSIONS
Gene transfection of HGF improved angiogenesis, thereby improved regional myocardial function and perfusion in chronic ischemic myocardium. It indicates a potent therapeutic value of HGF gene transfection for chronic ischemic heart diseases such as myocardial infarction.
Ahmet
Ismayil
I
First Department of Surgery, Osaka University Medical School, Suita, Osaka, Japan.
Sawa
Yoshiki
Y
Yamaguchi
Takahiro
T
Matsuda
Hikaru
H
D000818:Animals; D002196:Capillaries / Q000502:physiology; D002908:Chronic Disease; D003326:Coronary Circulation / Q000502:physiology; D004285:Dogs; D018014:Gene Transfer Techniques; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008081:Liposomes; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000473:pathology* / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D014162:Transfection
D008081:Liposomes; D017228:Hepatocyte Growth Factor