In vivo angiogenic activity and hypoxia induction of heterodimers of placenta growth factor vascular endothelial growth factor
In vivo angiogenic activity and hypoxia induction of heterodimers of placenta growth factor vascular endothelial growth factor
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DOI：
10.1172/jci119069
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发表时间：
1996-12-01
影响因子：
15.9
通讯作者：
Folkman, J
中科院分区：
文献类型：
--
作者：
Cao, YH;Linden, P;Folkman, J
为探讨胎盘生长因子（PlGF）及其与血管内皮生长因子（VEGF）异源二聚体的体内血管生成活性，研究了这些因子在小鼠角膜中诱导新生血管的作用。VEGF（165）足以刺激角膜缘血管的新毛细血管生长。PIGF（129）/VEGF（165）异二聚体也诱导角膜新生血管形成，其最大血管长度与VEGF（165）相似，但血管密度显著降低。相比之下，PlGF（129）在该体内血管生成测定中几乎没有作用或没有作用。低氧可显著上调绒毛膜癌细胞VEGF mRNA和蛋白的表达，而低氧对PIGF的表达无明显影响。VEGF产生的上调导致这些肿瘤细胞中PIGF/VEGF异二聚体的形成增加。因此，缺氧间接上调PIGF/VEGF异二聚体的表达水平，并在这些因子共表达时调节VEGF活性。
To investigate the in vivo angiogenic activity of placenta growth factor (PIGF) and its heterodimers with vascular endothelial growth factor (VEGF), the induction of neovascularization of these factors in the mouse cornea was studied. VEGF(165) is sufficiently potent to stimulate new capillary growth from the limbal vessels. PIGF(129)/VEGF(165) heterodimers also induce corneal neovascularization with a maximal vessel length similar to VEGF(165), but with a marked decrease of vessel density. In contrast, PIGF(129) has little or no effect in this in vivo angiogenesis assay. The expression of VEGF mRNA and protein is drastically up-regulated by hypoxia in choriocarcinoma cells, whereas expression of PIGF is not affected by the low concentration of oxygen. Up-regulation of VEGF production results in increased formation of PIGF/VEGF heterodimers in these tumor cells. Thus, hypoxia indirectly up-regulates expression levels of PIGF/VEGF heterodimers and modulates VEGF activity when these factors are co-expressed.