Combined administration of naked DNA vectors encoding VEGF and bFGF enhances tissue perfusion and arteriogenesis in ischemic hindlimb
Combined administration of naked DNA vectors encoding VEGF and bFGF enhances tissue perfusion and arteriogenesis in ischemic hindlimb
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DOI：
10.1016/j.bbrc.2007.06.120
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发表时间：
2007-09-07
影响因子：
3.1
通讯作者：
Kim, Duk-Kyung
中科院分区：
文献类型：
--
作者：
Lee, Jung-Sun;Kim, Jeong-Min;Kim, Duk-Kyung
很少有研究详细研究血管内皮生长因子 (VEGF) 和碱性成纤维细胞生长因子 (bFGF) 基因传递对侧枝发育的综合影响。在这里，我们使用基于骨骼肌的离体血管生成测定评估了编码 VEGF 和 bFGF 的裸 DNA 载体的潜在协同作用，并比较了后肢缺血小鼠模型中的组织灌注和肢体损失。在离体血管生成实验中，VEGF+bFGF组合组比LacZ、VEGF和bFGF组具有更大的毛细血管出芽面积。与这些结果一致，第 14 天的局部血流恢复在 VEGF+bFGF 组合组中也最高，其次是 bFGF、VEGF 和 LacZ 组。联合组的肢体丧失频率为0%，而其他组的肢体丧失频率为7-29%。联合组的缺血肌肉显示出血管生成和动脉生成增加的证据，以及可能与动脉生成相关的基因表达上调，例如心脏锚蛋白重复蛋白、早期生长反应因子-1和转化生长因子-β1的基因表达。我们的研究对血管闭塞性疾病联合基因疗法的开发具有重要意义。 (c) 2007 Elsevier Inc. 保留所有权利。
Few studies have examined in detail the combined effects of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene delivery on collateral development. Here, we evaluated the potential synergism of naked DNA vectors encoding VEGF and bFGF using a skeletal-muscle based ex vivo angiogenesis assay and compared tissue perfusion and limb loss in a murine model of hindlimb ischemia. In the ex vivo angiogenesis assay, the VEGF+bFGF combination group had a larger capillary sprouting area than those of the LacZ, VEGF, and bFGF groups. Consistent with these results, regional blood flow recovery on day 14 was also highest in the VEGF+bFGF combination group, followed by the bFGF, VEGF, and LacZ groups. The limb loss frequency was 0% in the combination group, whereas the limb loss frequencies of the other groups were 7-29%. The ischemic muscles of the combination group revealed evidence of increased angiogenesis and arteriogenesis and the upregulated expression of genes that may be associated with arteriogenesis, such as those for cardiac ankyrin repeat protein, early growth response factor-1, and transforming growth factor-beta 1. Our study has implications for the development of a combined gene therapy for the vascular occlusive diseases. (c) 2007 Elsevier Inc. All rights reserved.