Effect of Terplex/VEGF-165 gene therapy on left ventricular function and structure following myocardial infarction VEGF gene therapy for myocardial infarction
Effect of Terplex/VEGF-165 gene therapy on left ventricular function and structure following myocardial infarction VEGF gene therapy for myocardial infarction
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DOI：
10.1016/j.jconrel.2003.06.002
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发表时间：
2003-12-05
影响因子：
10.8
通讯作者：
Kim, SW
中科院分区：
文献类型：
--
作者：
Bull, DA;Bailey, SH;Kim, SW
背景：我们利用一种新型的脂多糖基因递送系统TeplexDNA，将血管内皮生长因子-165(VEC-165)载体导入兔冠状动脉结扎后的心肌，观察其对冠状动脉结扎后左心功能和结构的保护作用。方法：新西兰大白兔在直接心肌内注射Terplex或Terplex+50mug pVEGF-165后，行回旋支冠状动脉结扎术。超声心动图和组织学检查(n=12/组)。死亡率在不同组之间没有差异。数据以平均+/-标准差的形式报告。结果：在冠状动脉结扎后21天，pVEGF-165治疗的动物在短轴缩短率(20-25%，p=0.02)、长轴二维射血分数(42-51%，p=0.02)和短轴m型射血分数(46-54%，p=0.02)方面均有显著改善。对照组未见明显改善。接受血管内皮生长因子治疗的动物的梗死区周围血管密度增加了50%，并且有缩小梗死区面积的趋势(20%比29%，p=0.10)。在接受pVEGF-165治疗的动物中，舒张期心室面积从结扎前的1.87+/-0.24厘米(2)增加到结扎后21天的2.19+/-0.23厘米(2)，而对照组动物在同一时期从1.84+/-0.38增加到2.54+/-0.55厘米(2)(p=0.03)。同样，血管内皮生长因子-165组动物的心脏收缩面积从结扎前的1.06+/-0.26厘米(2)增加到结扎后21天的1.50+/-0.29厘米(2)，而对照组动物在同一时期从1.16+/-0.30增加到1.86+/-0.43厘米(2)(p=0.04)。结论：冠状动脉闭塞时给予TerplexDNA介导的血管内皮细胞生长因子载体可以改善心肌梗死后的左心功能，减少左心室的扩张。(C)2003爱思唯尔B.V.保留所有权利。
Background: We used a novel lipopolymeric gene delivery system, TeplexDNA, to transfect myocardium with plasmid vascular endothelial growth factor-165 (pVEGF) and evaluated the ability of pVEGF to preserve left ventricular function and structure after coronary ligation in a rabbit model. Methods: New Zealand white rabbits underwent circumflex coronary ligation after direct intramyocardial injection of either Terplex alone or Terplex+50 mug pVEGF-165. Serial echocardiography and histologic studies were performed (n=12/group). Mortality did not differ between groups. The data is reported as the mean+/-standard deviation. Results: Over the 21 days following coronary ligation, pVEGF-165-treated animals demonstrated significant improvement in fractional shortening (20-25%, p = 0.02), long axis two-dimensional ejection fraction (42-51%, p = 0.02) and short axis m-mode ejection fraction (46-54%, p = 0.02). No significant improvements were noted in the control group. VEGF-treated animals had a 50% increase in peri-infarct vessel density and a trend towards a smaller infarct size (20% vs. 29%, p = 0.10). In animals receiving pVEGF-165, the diastolic ventricular area increased from 1.87+/-0.24 cm(2) prior to ligation to 2.19+/-0.23 cm(2) at 21 days following ligation, compared to an increase from 1.84+/-0.38 to 2.54+/-0.55 cm(2) over the same period in control animals (p = 0.03). Similarly, the systolic ventricular area in VEGF-165 animals increased from 1.06+/-0.26 cm(2) prior to ligation to 1.50+/-0.29 cm(2) at 21 days following ligation, compared to an increase from 1.16+/-0.30 to 1.86+/-0.43 cm(2) over the same period in the control animals (p = 0.04). Conclusion: TerplexDNA mediated delivery of plasmid VEGF administered at the time of coronary occlusion improves left ventricular function and reduces left ventricular dilation following myocardial infarction. (C) 2003 Elsevier B.V All rights reserved.