A study on the regulation of angiogenesis by novel substance derived from marine algae

海藻新物质调控血管生成的研究

• 批准号: 06672285
• 负责人: ASHINO Hiromi
• 金额: $ 1.28万
• 依托单位: The Tokyo Metropolitan Institute of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672285/
• 关键词: Angiogenesis; Vascular endothelial cells; Sulfated polysaccharides; Marine algae; Tubu formation; Angiogenic inhibitor; FGF; Migration

Angiogenesis, the process of new capillary formation, participates in numerous physiological events, both normal and pathological. A number of serious diseases are dominated by abnormal neovascularization, including solid tumor growth and metastasis, diabetic retinopaathy and rheumatoid arthritis. The potential therapeutic benefit that a naturally occuring inhibitor of angiogenesis might have in controlling diseases in which neovascularization is involved has prompted a search for angiogenesis inhibitors.Certain tissues such as cartilage are resistant to vascular invasion. Cartilage has various and much of acidic polysaccharides, and angiogenic (stimulatory) factor, such as FGF,might be regulated by heparan sulfate. Moreover, angiogenesis begin from the triggering that an angiogenic factor activates vascular endothelial cells, therefore the suppression of trigger is important, as compared with inhibition of each step of angiogenesis. Acidic polysaccharides might be candidate for angige … More nic inhibitor. We examined the inhibitory effect of various acidic polysaccharides from all kinds of marine algae, which are rich sources of them, the inhibitory behavior, the effect for FGF function and the regulatory mechanism of them, on angiogenesis.The results obtained showed the following : (1) Fucoidan from brown algae markedly showed an inhibitory activity of angiogenesis and porphyran showed a weak activity. Among of acidic polysaccharides from five unknown monocellular algae in marine, we could find two polysaccharides which show the strong inhibition on angiogenesis ; (2) Both of porphyran and dextran sulfate markedly suppressed the migration and tube formation in vitro, even in the induced condition by FGF ; (3) Both of inhibition of angiogenesis in vivo and migration in vitro by acidic polysaccharides depend on sulfate contents ; (4) Sulfated polysaccharides enhanced the adhesion for culture plates ; (5) We succeeded to get the low molecular and active porphyran on the inhibition of angiogenesis without anti-blood coagulation function ; (6) In the structure unknownacidic polysaccharides from monocellular algae in marine which we found, it was suggested that sulfate contents is important in the exertion of anti-angiogenic function.These data suggest that the functional point of angiogenic inhibition by acidic polysaccharides is the suppression of activation of vascular endothelial cells by angiogenic factor. Less

血管生成，即新毛细血管形成的过程，参与许多正常和病理的生理事件。许多严重疾病都是由异常的新生血管支配的，包括实体瘤的生长和转移、糖尿病视网膜病变和类风湿性关节炎。天然存在的血管生成抑制剂在控制涉及新血管形成的疾病方面可能具有潜在的治疗益处，这促使人们寻找血管生成抑制剂。某些组织（例如软骨）对血管侵袭具有抵抗力。胡萝卜素含有种类繁多的酸性多糖，硫酸乙酰肝素可能对血管生成（刺激）因子（如FGF）有调节作用。此外，血管生成开始于血管生成因子激活血管内皮细胞的触发，因此与抑制血管生成的每个步骤相比，抑制触发是重要的。酸性多糖可能是血管生成的候选者 ...更多信息 nic抑制剂本实验研究了来源丰富的各种海藻酸性多糖对血管生成的抑制作用、抑制行为、对FGF功能的影响及其调控机制，结果表明：（1）褐藻岩藻聚糖硫酸酯具有明显的血管生成抑制活性，而卟啉具有较弱的血管生成抑制活性。在5种未知单细胞海藻的酸性多糖中，发现有两种多糖对血管生成有较强的抑制作用：（2）卟啉和硫酸葡聚糖在体外均能显著抑制血管的迁移和小管形成，即使在FGF诱导的条件下也是如此：（3）酸性多糖对体内血管生成的抑制和体外血管的迁移均依赖于硫酸根含量;（4）硫酸化多糖对培养板的粘附性有增强作用：（5）我们成功地得到了低分子量的、具有抑制血管生成活性的卟啉，而没有抗凝血功能;（6）在所发现的海洋单细胞藻酸性多糖中，说明硫酸盐含量在抗氧化能力的发挥中起重要作用。这些数据表明，酸性多糖抑制血管生成的功能点是抑制血管内皮细胞被血管生成抑制剂激活。因子少

项目成果

Hiromo Ashino: "Inhibition of angiogenesis by diisopropyl fluorophosphate." Recent Advances in Chemotherapy. 18. 867-868 (1994)

Hiromo Ashino：“氟磷酸二异丙酯抑制血管生成。”

Mariko Shimamura: "Actinonin, an enzyme inhibitor that inhibits angiogenesis suppresses tumor metastasis." International Committee on Proteolysis. 10. 133 (1994)

Mariko Shimamura：“放线菌素是一种抑制血管生成的酶抑制剂，可抑制肿瘤转移。”

Mariko Shimamura: "Suppression of tumor metastasis by enzyme inhibitor with antiangiogenic activity." Can. J. Infect. Dis.6Suppl. C. 298 (1995)

Mariko Shimamura：“通过具有抗血管生成活性的酶抑制剂抑制肿瘤转移。”

Hiromi, Ashino: "Serine protease inhibitors suppress angiogenesis." International Committee on Proteolysis. 10. 132 (1994)

Hiromi, Ashino：“丝氨酸蛋白酶抑制剂抑制血管生成。”

Hiromo Ashino: "Anti-angiogenic activity of ascorbic acid and its derivatives." Can. J. Infect. Dis.6Suppl. C. 393 (1995)

Hiromo Ashino：“抗坏血酸及其衍生物的抗血管生成活性。”