Genetic background influences therapeutic effectiveness of VEGF
Genetic background influences therapeutic effectiveness of VEGF
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DOI：
10.1016/j.bbrc.2003.08.134
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发表时间：
2003-10-10
影响因子：
3.1
通讯作者：
Nagai, R
中科院分区：
文献类型：
--
作者：
Fukino, K;Sata, M;Nagai, R
治疗性血管生成已成为一种有前途的治疗方法，但有些患者是难治性的外源性生长因子。为了确定出生后血管生成和生理性血管形成的遗传决定因素，我们研究了影响缺血诱导的小鼠侧枝发育的遗传因素。在C57 BL/6、C3 H/He中建立后肢缺血模型。和BALB/c小鼠。通过缺血肌肉的血液灌注和毛细血管密度的恢复来确定小鼠之间的血管生成是显着不同的。BALB/c小鼠侧支血管形成受损与血管内皮细胞生长因子（VEGF）表达减少有关。肌内注射VEGF基因可促进C57 BL/6 J小鼠侧支形成，但对BALB/c小鼠侧支形成无明显影响。BALB/c小鼠中VEGF的无效与VEGF受体表达受损相关。我们的研究结果表明，遗传背景可能会影响自发侧支形成和外源性VEGF的治疗效果。在某些患者中，可能需要除了单独给予VEGF之外的替代策略来实现最佳血管生成。(C)2003年爱思唯尔公司All rights reserved.
Therapeutic angiogenesis has emerged as a promising therapy, but some patients are refractory to exogenous growth factors. In order to identify the genetic determinants of post-natal angiogenesis and physiological vessel formation, we investigated the genetic factors that affected ischemia-induced development of collaterals in mice. An ischemic hindlimb model was generated in C57BL/6, C3H/He. and BALB/c mice. Angiogenesis was markedly different among the mice as determined by the restoration of blood perfusion and capillary density of the ischemic muscle. Impaired collateral vessel formation in BALB/c mice was associated with reduced expression of vascular endothelial cell growth factor (VEGF). Intramuscular gene transfer of VEGF promoted collateral formation in C57BL/6J mice, but not in BALB/c mice. Ineffectiveness of VEGF in BALB/c mice was associated with impaired expression of VEGF receptor. Our findings suggest that genetic background may influence spontaneous collateral formation and therapeutic effectiveness of exogenous VEGF. Alternative strategies other than administration of VEGF alone might be needed to attain optimal angiogenesis in some patients. (C) 2003 Elsevier Inc. All rights reserved.