Induction of collateral artery growth and improvement of post-infarct heart function by hepatocyte growth factor gene transfer.
OBJECTIVE
To study the effect of adenovirus5-mediated human hepatocyte growth factor (Ad(5)-HGF) transfer on post-infarct heart failure in a swine model.


METHODS
Twelve young Suzhong swine were randomly divided into 2 groups: the Ad(5)-HGF group (n=6) and the null-Ad(5) group (n=6). Four weeks after left anterior descending coronary artery (LAD) ligation, Ad5-HGF was transferred into the myocardium via the right coronary artery. Coronary angiography and gated cardiac perfusion imaging were performed at the end of 4 and 7 weeks after LAD ligation, respectively, to evaluate collateral artery growth and cardiac perfusion. Then all animals were killed, the expression of HGF and alpha-smooth muscle actin (alpha-SMA) were evaluated by enzyme-linked immunosorbent assay and immunohistochemistry.


RESULTS
Compared with the null-Ad(5) group, higher expression of human HGF was observed in the myocardium in the Ad(5)-HGF group (109.3+/-7.8 vs 6.2+/-2.6, t=30.685, P<0.01). The left ventricular ejection fraction was higher in the Ad(5)-HGF group than in the null-Ad(5) group (43.9+/-4.3 vs 30.4+/-2.8, t=6.514, P<0.01). From the 4th week to the 7th week after operation, left ventricular end systolic volume (42.1+/-3.0 vs 31.0+/-4.9, t=12.800, P<0.01) and left ventricular end diastolic volume (62.2+/-4.2 vs 55.0+/-4.8 t=13.207, P<0.01) were improved in the Ad(5)-HGF group. Cardiac perfusion was significantly improved in the Ad(5)-HGF group. In the Ad(5)-HGF group, growth of collateral arteries was obviously greater (average rank sum 9.17 vs 3.83, n=6, u=-2.687, P<0.01), and the number of alpha-SMA(+) vessels/mm(2) was significantly greater (56.1+/-4.2 vs 16.4+/-3.5, t=17.731, P<0.01) than in the null-Ad(5) group.


CONCLUSIONS
High expression levels of human HGF were observed in the myocardium because of non-infarct-related vessel transfer. HGF can increase the number of functional arterioles and improve collateral artery growth. HGF can improve cardiac perfusion and heart function.
Wang
Wei
W
Department of Cardiovascular Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yang
Zhi-Jian
ZJ
Ma
Dong-Chao
DC
Wang
Lian-Sheng
LS
Xu
Shun-Lin
SL
Zhang
You-Rong
YR
Cao
Ke-Jiang
KJ
Zhang
Fu-Min
FM
Ma
Wen-Zhu
WZ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001158:Arteries / Q000502:physiology; D001160:Arterioles / Q000503:physiopathology; D003097:Collateral Circulation; D003331:Coronary Vessels / Q000503:physiopathology; D018014:Gene Transfer Techniques; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011897:Random Allocation; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine
D017228:Hepatocyte Growth Factor