VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) INDUCES PLASMINOGEN ACTIVATORS AND PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN MICROVASCULAR ENDOTHELIAL-CELLS
VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) INDUCES PLASMINOGEN ACTIVATORS AND PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN MICROVASCULAR ENDOTHELIAL-CELLS
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DOI：
10.1016/0006-291x(91)91276-i
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发表时间：
1991-12-16
影响因子：
3.1
通讯作者：
MONTESANO, R
中科院分区：
文献类型：
--
作者：
PEPPER, MS;FERRARA, N;MONTESANO, R
细胞外蛋白水解被认为是血管生成过程的重要组成部分。研究人员评估了血管生成因子VEGF对微血管内皮细胞中PA活性以及PA和PAI-1 mRNA水平的影响。VEGF增加u-PA和t-PA活性呈剂量依赖性，在30ng/ml时最大。暴露于VEGF 15小时后，u-PA和t-PA mRNA分别增加7.5倍和8倍，PAI-1 mRNA增加4.5倍。在等摩尔浓度（0.5nM）下，VEGF对t-PA mRNA的诱导作用强于bFGF，而bFGF对u-PA和PAI-1 mRNA的诱导作用强于bFGF。此外，VEGF诱导u-PA和PAI-1 mrna的动力学与先前在bFGF中证实的相似。这些结果表明，在微血管内皮细胞中，VEGF对PA和PAI-1的产生有调节作用，并与正常毛细血管形态发生需要蛋白酶抑制剂适当平衡的细胞外蛋白水解的假设相一致。
Extracellular proteolysis is believed to be an essential component of the angiogenic process. The effects of VEGF, a recently described angiogenic factor, were assessed on PA activity and PA and PAI-1 mRNA levels in microvascular endothelial cells. u-PA and t-PA activity were increased by VEGF in a dose-dependent manner, with maximal induction at 30ng/ml. u-PA and t-PA mRNAs were increased 7.5- and 8-fold respectively after 15 hours, and PAI-1 mRNA 4.5-fold after 4 hours exposure to VEGF. At equimolar concentrations (0.5nM), VEGF was a more potent inducer of t-PA mRNA than bFGF, while bFGF was a more potent inducer of u-PA and PAI-1 mRNAs. In addition, VEGF induced u-PA and PAI-1 mRNAs with kinetics similar to those previously demonstrated for bFGF. These results demonstrate the regulation of PA and PAI-1 production by VEGF in microvascular endothelial cells and are in accord with the hypothesis that extracellular proteolysis, appropriately balanced by protease inhibitors, is required for normal capillary morphogenesis.