VEGF gene delivery to muscle: Potential role for vasculogenesis in adults

VEGF gene delivery to muscle: Potential role for vasculogenesis in adults
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DOI:
10.1016/s1097-2765(00)80154-9
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发表时间:
1998-11-01
期刊:
影响因子:
16
通讯作者:
Blau, HM
Blau, HM
中科院分区:
生物学1区
文献类型:
--
作者:
Springer, ML;Chen, AS;Blau, HM

文献摘要

被引文献

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将基因工程成肌细胞植入非缺血肌肉后,VEGF的组成型表达导致血管结构增加。以前,VEGF递送至成人肌肉的作用仅在缺血组织中报道。由此产生的血管结构让人想起那些在胚胎血管发生过程中形成的,而不是血管生成,从预先存在的血管发芽。最初,VEGF引起内皮细胞和巨噬细胞的积累,随后血管通道和血管瘤的网络与局部高血清VEGF水平。在检测到低血清VEGF的邻近组织或对侧腿中没有明显影响。这些数据表明,VEGF诱导血管生成或血管发生可能是剂量依赖性的。此外,VEGF的表达必须小心调节,因为过度表达是有害的。
Constitutive expression of VEGF after implantation of genetically engineered myoblasts into non-ischemic muscle led to an increase in vascular structures. Previously, effects of VEGF delivery to adult muscle have only been reported in ischemic tissues. The resulting vascular structures were reminiscent of those formed during embryonic vasculogenesis, rather than angiogenesis, sprouting from preexisting vessels. Initially, VEGF caused an accumulation of endothelial cells and macrophages, followed by networks of vascular channels and hemangiomas with locally high serum VEGF levels. No effects were evident in adjacent tissue or contralateral legs, where low serum VEGF was detected. These data suggest that the induction by VEGF of angiogenesis or vasculogenesis may be dose-dependent. Furthermore, VEGF expression must be carefully modulated, as overexpression is deleterious.