Induction of collateral artery growth and improvement of post-infarct heart function by hepatocyte growth factor gene transfer

Abstract

Aim: 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.

Conclusion: 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.