Therapeutic angiogenesis in the ischemic canine heart induced by myocardial injection of naked complementary DNA plasmid encoding hepatocyte growth factor
Therapeutic angiogenesis in the ischemic canine heart induced by myocardial injection of naked complementary DNA plasmid encoding hepatocyte growth factor
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DOI：
10.1067/mtc.2002.123809
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发表时间：
2002-12-01
影响因子：
6
通讯作者：
Matsuda, H
中科院分区：
文献类型：
--
作者：
Funatsu, T;Sawa, Y;Matsuda, H
目的：我们研究了将编码人肝细胞生长因子的互补DNA质粒直接注射到缺血的犬心肌中以诱导血管生成的功效。结扎左冠状动脉前降支4周后，将125 μ g编码肝细胞生长因子（n = 8）或LacZ基因的互补DNA质粒（转染对照组，n = 8）直接注射到正常组织和梗塞之间的边界处的心肌中。另外8只狗被用作假手术对照组。在转染前和转染后4周，在多巴酚丁胺给药下评价正常（回旋支分支区域）和缺血区域的区域增厚分数（表明收缩功能）和血流。处死动物，并评估两个区域的毛细血管数量。这些数据在缺血区进行了评价，作为那些在normal.Results的百分比：在缺血区的心肌毛细血管的数量成功地增加到约140%，通常在肝细胞生长因子组，而没有变化被观察到在其他组（P = 0.0017的方差分析）。此外，局部增厚分数和缺血区的血流量，在冠状动脉结扎后恶化，肝细胞生长因子组相对于其他组显示出显着改善（通过方差分析，增厚分数P <0.0001，通过方差分析，血流量P = 0.0005）。这些结果支持直接注射编码人肝细胞生长因子的质粒互补DNA诱导缺血心肌中治疗性血管生成的功效。
Objective: We investigated the efficacy of directly injecting a plasmid with complementary DNA encoding human hepatocyte growth factor into ischemic canine myocardium to induce angiogenesis.Methods: Four weeks after ligation of the left anterior descending coronary artery, 125 mug of a complementary DNA plasmid encoding the gene for either hepatocyte growth factor (n = 8) or LacZ (transfection control group, n = 8) was injected directly into the myocardium at the border between the normal tissue and the infarction. Eight other dogs were used as a sham control group. Regional thickening fraction, which indicated contractile function, and blood flow in the normal (circumflex branch territory) and ischemic areas were evaluated under dobutamine administration just before and 4 weeks after transfection. The animals were killed, and capillary numbers in both areas were assessed. These data in the ischemic area were evaluated as the percentage of those in the normal.Results: The number of myocardial capillaries in the ischemic area was successfully increased to approximately 140% of usual in the hepatocyte growth factor group, whereas no change was observed in the other groups (P = .0017 by analysis of variance). Furthermore, regional thickening fraction and blood flow in the ischemic area, which had deteriorated after coronary ligation, showed significant improvement in the hepatocyte growth factor group relative to the other groups (thickening fraction P < .0001 by analysis of variance, blood flow P = .0005 by analysis of variance).Conclusions: These results support the efficacy of the direct injection of plasmid complementary DNA encoding human hepatocyte growth factor to induce therapeutic angiogenesis in the ischemic myocardium.