Induction of collateral artery growth and improvement of post-infarct heart function by hepatocyte growth factor gene transfer
Induction of collateral artery growth and improvement of post-infarct heart function by hepatocyte growth factor gene transfer
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DOI：
10.1111/j.1745-7254.2006.00306.x
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发表时间：
2006-05
影响因子：
8.2
通讯作者：
Wei Wang;Zhijian Yang;Dong-chao Ma;Liansheng Wang;Shun-lin Xu;You-rong Zhang;K. Cao;Fu-min Zhang;Wen-zhu Ma
中科院分区：
文献类型：
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作者：
Wei Wang;Zhijian Yang;Dong-chao Ma;Liansheng Wang;Shun-lin Xu;You-rong Zhang;K. Cao;Fu-min Zhang;Wen-zhu Ma
目的：研究腺病毒5型（Ad 5）介导的人肝细胞生长因子（HGF）对猪心肌梗死后心力衰竭的影响，方法：12头幼年苏忠猪随机分为Ad 5 HGF组（n=6）和Ad 5空白组（n=6）。结扎左冠状动脉前降支（LAD）4周后，经右冠状动脉将Ad 5-HGF转染心肌。分别于结扎后4周和7周行冠状动脉造影及门控心脏灌注显像，评价侧支动脉生长情况和心脏灌注情况。结果：Ad 5-HGF组心肌组织中HGF的表达明显高于null-Ad 5组（109.3± 7.8vs6.2 ±2.6，t=30.685，P<0.01）; Ad 5-HGF组左室射血分数高于null-Ad 5组（43.9± 4.3vs30.4 ±2.8，t=6.514，P<0.01）。术后4 ~ 7周，Ad 5-HGF组左室收缩末容积（42.1±3.0 vs 31.0±4.9，t=12.800，P<0.01）和左室舒张末容积（62.2±4.2 vs 55.0±4.8，t=13.207，P<0.01）均较术前明显改善。Ad 5-HGF组心脏灌注明显改善。Ad 5-HGF组侧支动脉生长明显大于Ad 5-HGF组（平均秩和9.17 vs 3.83，n=6，u=-2.687，P<0.01），α-SMA+血管数量/mm 2明显更多（56.1± 4.2vs16.4 ±3.5，t=17.731，P<0.01）。结论：非梗死相关血管转移可导致心肌组织中HGF的高表达。HGF可增加功能性小动脉数目，促进侧支动脉生长。HGF可改善心脏灌注和心功能。
AbstractAim:To study the effect of adenovirus5-mediated human hepatocyte growth factor (Ad5-HGF) transfer on post-infarct heart failure in a swine model.Methods:Twelve young Suzhong swine were randomly divided into 2 groups: the Ad5-HGF group (n=6) and the null-Ad5 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 α-smooth muscle actin (α-SMA) were evaluated by enzyme-linked immunosorbent assay and immunohistochemistry.Results:Compared with the null-Ad5 group, higher expression of human HGF was observed in the myocardium in the Ad5-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 Ad5-HGF group than in the null-Ad5group (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 Ad5-HGF group. Cardiac perfusion was significantly improved in the Ad5-HGF group. In the Ad5-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 α-SMA+ vessels/mm2 was significantly greater (56.1±4.2 vs 16.4±3.5, t=17.731, P<0.01) than in the null-Ad5 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.