三联/VEGF-165基因疗法对心肌梗死后左心室功能和结构的影响。用于心肌梗死的VEGF基因疗法。

Effect of Terplex/VEGF-165 gene therapy on left ventricular function and structure following myocardial infarction. VEGF gene therapy for myocardial infarction.

作者信息

Bull David A, Bailey Stephen H, Rentz Jeffrey J, Zebrack James S, Lee Minhyung, Litwin Sheldon E, Kim Sun Wan

机构信息

Division of Cardiothoracic Surgery, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA.

出版信息

J Control Release. 2003 Dec 5;93(2):175-81. doi: 10.1016/j.jconrel.2003.06.002.

DOI:10.1016/j.jconrel.2003.06.002

PMID:14636723

Abstract

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 microg 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 cm2 prior to ligation to 2.19 +/- 0.23 cm2 at 21 days following ligation, compared to an increase from 1.84 +/- 0.38 to 2.54 +/- 0.55 cm2 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 cm2 prior to ligation to 1.50 +/- 0.29 cm2 at 21 days following ligation, compared to an increase from 1.16 +/- 0.30 to 1.86 +/- 0.43 cm2 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.

摘要

背景

我们使用了一种新型的脂质聚合物基因递送系统TeplexDNA，将质粒血管内皮生长因子-165（pVEGF）转染至心肌，并在兔模型中评估了pVEGF在冠状动脉结扎后维持左心室功能和结构的能力。

方法

新西兰白兔在直接心肌内注射单独的Terplex或Terplex + 50微克pVEGF-165后进行冠状动脉结扎。进行了系列超声心动图和组织学研究（每组n = 12）。两组间死亡率无差异。数据以平均值±标准差表示。

结果

在冠状动脉结扎后的21天内，接受pVEGF-165治疗的动物在缩短分数（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）方面有显著改善。对照组未观察到显著改善。接受VEGF治疗的动物梗死周边血管密度增加50%，梗死面积有减小趋势（20%对29%，p = 0.10）。在接受pVEGF-165的动物中，舒张期心室面积从结扎前的1.87±0.24平方厘米增加至结扎后21天的2.19±0.23平方厘米，而同期对照组动物从1.84±0.38平方厘米增加至2.54±0.55平方厘米（p = 0.03）。同样，VEGF-165组动物收缩期心室面积从结扎前的1.06±0.26平方厘米增加至结扎后21天的1.50±0.29平方厘米，而同期对照组动物从1.16±0.30平方厘米增加至1.86±0.43平方厘米（p = 0.04）。