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A PRODUCTIVE TRIAL OF ANTI-ANGIGENIC AGENTS BASED ON A ELUCIDATION OF A MECHANISM OF bFGF AS A FIRST TRIGGER ON ANGIOGENIC PATHWAY

基于阐明 bFGF 作为血管生成途径第一触发因素的机制的抗血管生成药物的富有成效的试验

基本信息

批准号：
09672343
负责人：
ASHINO Hiromi
金额：
$ 1.66万
依托单位：
TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672343/
关键词：
Angiogenesis Acidic polysaccharides bFGF Herapan sulfate chorioallantoic membrane endothelial cells bFGF FGF

项目摘要

In order to try the production of inhibitors of angiogenic diseases, which inhibit the activity of first angiogenic factor functioning as a trigger, we examined anti-angiogenic activities of various acidic polysaccharides using chick embryonic chorioallantoic membrane (CAM)s and bovine vascular endothelial cell culture.We found that Dextran sulfate (DS) markedly inhibited angiogenesis of chick CAMs, that its inhibitory effect did not depend on molecular weight, but depended on sulfation, that DS inhibited cell migration unstimulated and stimulated by bFGF and that in heparitinase-treated endothelial cells the signal of bFGF to induce plasminogen activator was weakened.These results indicate that DS may disrupt binding of bFGF or heparin / heparan sulfate(HS)-binding angiogenic factors to HS, resulting in the inhibition of angiogenesis. It is thought that functional inhibition of angiogenic factor as a trigger is important and effective to suppress the initiation of angiogenesis. Accordingly molecules like DS that modulate the activity of heparin / HS-binding growth factors by sequestering the growth factor are expected to suppress the early step of angiogenesis.

为了尝试制备血管生成疾病的抑制剂，抑制作为触发因子的第一血管生成因子的活性，我们用鸡胚毛囊尿囊膜（CAM）和牛血管内皮细胞培养物检测了各种酸性多糖的抗血管生成活性。结果表明，硫酸葡聚糖（Dextran sulfate， DS）对鸡CAMs血管生成有明显的抑制作用，其抑制作用不依赖于分子量，而依赖于硫酸酸化，对bFGF未刺激和刺激的细胞迁移均有抑制作用，肝素酶处理的内皮细胞中bFGF诱导纤溶酶原激活物的信号减弱。这些结果表明，DS可能破坏bFGF或肝素/硫酸肝素（HS）结合的血管生成因子与HS的结合，从而抑制血管生成。认为血管生成因子的功能性抑制是抑制血管生成的重要和有效的触发因素。因此，像DS这样通过隔离生长因子来调节肝素/ hs结合生长因子活性的分子有望抑制血管生成的早期阶段。