VASCULAR ENDOTHELIAL GROWTH-FACTOR INDUCED BY HYPOXIA MAY MEDIATE HYPOXIA-INITIATED ANGIOGENESIS
VASCULAR ENDOTHELIAL GROWTH-FACTOR INDUCED BY HYPOXIA MAY MEDIATE HYPOXIA-INITIATED ANGIOGENESIS
复制标题
DOI：
10.1038/359843a0
复制
发表时间：
1992-10-29
期刊：
影响因子：
64.8
通讯作者：
KESHET, E
中科院分区：
文献类型：
--
作者：
SHWEIKI, D;ITIN, A;KESHET, E
血管供应不足和由此导致的组织氧分压降低通常会导致新生血管形成，以满足组织的需要1。例子包括缺血组织中侧支血管的代偿性发育，否则这些血管对于血管生成和与缺氧伤口愈合相关的血管生成是静止的2。但缺氧诱导的血管生成因子介导的反馈反应尚未确定。在这里，我们表明，血管内皮生长因子（VEGF，也被称为血管通透性因子）可能作为一个缺氧诱导的血管生成因子。VEGF信使RNA水平在将不同细胞培养物暴露于缺氧的几小时内显著增加，并且当恢复正常氧气供应时恢复到背景。进行新血管形成的肿瘤标本的原位分析表明，VEGF的产生是专门诱导的胶质母细胞瘤细胞的一个子集，其区别是直接接近坏死灶（大概是缺氧区域）和聚集的毛细血管旁边的VEGF产生细胞。
INEFFICIENT vascular supply and the resultant reduction in tissue oxygen tension often lead to neovascularization in order to satisfy the needs of the tissue1. Examples include the compensatory development of collateral blood vessels in ischaemic tissues that are otherwise quiescent for angiogenesis and angiogenesis associated with the healing of hypoxic wounds2. But the presumptive hypoxia-induced angiogenic factors that mediate this feedback response have not been identified. Here we show that vascular endothelial growth factor (VEGF; also known as vascular permeability factor) probably functions as a hypoxia-inducible angiogenic factor. VEGF messenger RNA levels are dramatically increased within a few hours of exposing different cell cultures to hypoxia and return to background when normal oxygen supply is resumed. In situ analysis of tumour specimens undergoing neovascularization show that the production of VEGF is specifically induced in a subset of glioblastoma cells distinguished by their immediate proximity to necrotic foci (presumably hypoxic regions) and the clustering of capillaries alongside VEGF-producing cells.