EXOGENOUS VASCULAR ENDOTHELIAL GROWTH-FACTOR INDUCES MALFORMED AND HYPERFUSED VESSELS DURING EMBRYONIC NEOVASCULARIZATION
EXOGENOUS VASCULAR ENDOTHELIAL GROWTH-FACTOR INDUCES MALFORMED AND HYPERFUSED VESSELS DURING EMBRYONIC NEOVASCULARIZATION
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DOI：
10.1073/pnas.92.17.7657
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发表时间：
1995-08-15
影响因子：
11.1
通讯作者：
LITTLE, CD
中科院分区：
文献类型：
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作者：
DRAKE, CJ;LITTLE, CD
血管内皮生长因子（VEGF）是一种有效且特异的内皮有丝分裂原，其能够在体内诱导血管生成[Leung，D. W.的，Cachianes，G.，匡，W.- J.，Goeddel，D.五、&费拉拉，N.（1989）Science 246 1306-1309]。为了确定VEGF是否也影响原始内皮细胞的行为，我们使用了基于血管从头形成的体内血管测定法。在血管发生开始时注射纳摩尔量的165-残基形式的VEGF的日本鹌鹑胚胎表现出显著改变的血管发育。事实上，在所有注射VEGF的胚胎中，血管网络的总体模式是异常的。畸形可归因于两种特定的内皮细胞活性：（i）在正常无血管区域中不适当的新血管形成和（ii）血管的不受调节的过度融合，首先，多余血管直接连接心脏的流入通道和主动脉流出通道。第二种异常活性导致具有异常大管腔的血管的形成。最终，不受调节的血管融合产生了大量的血管囊，其消除了个体血管的身份。这些观察结果表明外源性VEGF对参与血管发生的原始内皮细胞的行为具有影响，并且他们强烈地提示内源性VEGF在血管形成和血管大小的调节（管腔形成）中是重要的。
Vascular endothelial growth factor (VEGF) is a potent and specific endothelial mitogen that is able to induce angiogenesis in vivo [Leung, D. W., Cachianes, G., Kuang, W.-J., Goeddel, D. V., & Ferrara, N. (1989) Science 246 1306-1309]. To determine if VEGF also influences the behavior of primordial endothelial cells, we used an in vivo vascular assay based on the de novo formation of vessels. Japanese quail embryos injected with nanomolar quantities of the 165-residue form of VEGF at the onset of vasculogenesis exhibited profoundly altered vessel development, In fact, the overall patterning of the vascular network was abnormal in all VEGF-injected embryos, The malformations were attributable to two specific endothelial cell activities: (i) inappropriate neovascularization in normally avascular areas and (ii) the unregulated, excessive fusion of vessels, In the first instance, supernumerary vessels directly linked the inflow channel of the heart to the aortic outflow channel. The second aberrant activity led to the formation of vessels with abnormally large lumens, Ultimately, unregulated vessel fusion generated massive vascular sacs that obliterated the identity of individual vessels, These observations show that exogenous VEGF has an impact on the behavior of primordial endothelial cells engaged in vasculogenesis, and they strongly suggest that endogenous VEGF is important in vascular patterning and regulation of vessel size (lumen formation).