Recruitment of stem cells by hepatocyte growth factor via intracoronary gene transfection in the postinfarction heart failure.
We aim to study the amelioration effect of adenovirus5-mediated human hepatocyte growth factor gene transfer on postinfarction heart failure in swine model. Twelve Suzhong young swine were randomly divided into 2 groups of 6 pigs each: Ad(5)-HGF group and mock-vector Ad(5) group. Four weeks after ligation of the left anterior descending coronary artery, Ad(5)-HGF was intracoronarily transferred into the myocardium. Simultaneously, gate cardiac perfusion imaging was performed to evaluate the heart function. Three weeks later, gate cardiac perfusion imaging was performed again, then the hearts were removed and sectioned for immunohistochemical examination to illustrate the effects of Ad(5)-HGF on infarcted myocardium. The expression of HGF was examined by ELISA. The results were: (1) compared with the mock-vector Ad(5) group, high expression of human HGF was observed in the myocardium of Ad(5)-HGF group; (2) in the Ad(5)-HGF group, the number of CD117(+) cells co-expressing c-Met per mm(2) was significantly larger; (3) the improvement in LVEF was greater in the Ad(5)-HGF group than in the mock-vector Ad(5) group. We concluded that: (1) high expression of human HGF was observed in the myocardium through intracoronary gene transfection; (2) HGF can improve the mobilization of CD117(+)/c-Met(+) stem cells into ischemic myocardium. The amelioration effect of HGF on postinfarction heart failure could not be limited to stimulating angiogenesis, anti-apoptosis, anti-fibrosis, but was also involved in the recruitment of stem cells into myocardium.
Yang
ZhiJian
Z
Department of Cardiovascular Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. enzhijia@yahoo.com.cn
Wang
Wei
W
Ma
DongChao
D
Zhang
YouRong
Y
Wang
LianSheng
L
Zhang
YuQing
Y
Xu
ShunLin
S
Chen
Bo
B
Miao
DengShun
D
Cao
KeJiang
K
Ma
WenZhu
W
D000818:Animals; D002465:Cell Movement / Q000235:genetics; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000209:etiology / Q000473:pathology / Q000628:therapy; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism*; D013552:Swine; D014162:Transfection
C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; D019009:Proto-Oncogene Proteins c-kit