Regulation of angiogenesis-related diseases by conjugated trienoic acids, tocotrienol and amadori-glycated phospholipids.

共轭三烯酸、生育三烯酚和阿马多里糖化磷脂调节血管生成相关疾病。

• 批准号: 15380086
• 负责人: MIYAZAWA Teruo
• 金额: $ 9.6万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15380086/
• 关键词: angiogenesis inhibition; conjugated trienoic fatty acid; tocotrienol; glycated phosphatidylethanolamine; cancer; atherosclerosis; diabetic retinopathy; vascular endothelial cells

Angiogenesis is the process of generating new capillary blood vessels, involving proliferation of endothelial cells, cell migration, and capillary tube formation. Abnormal angiogenesis relates to intractable diseases such as cancer, diabetic retinopathy atherosclerosis, and arthritis. Therefore, the present, interestingly, the inhibition of angiogenesis is one of the most attractive approaches for prevention of these diseases. Moreover, regulation of angiogenesis by foods and food components is becoming an important issue.Our previous researches have shown that conjugated trienoic fatty acid and tocotrienol can inhibit angiogenesis more effectively than some medicinal drugs. Moreover, we have proved the presence of Amadori glycated phosphatidylethanolamine, a lipid-linked glycation compound, as accelerator of angiogenesis.In this study, 1)conjugated trienoic fatty acids were fed to nude mice with transplant of tumor cells and antitumor mechanism and anti-angiogenesis activity of conjugated trienoic fatty acids were investigated. 2)The anti-angiogenic mechanism of tocotrienol, a natural analog of tocopherol, was investigated both in vitro and in vivo. 3)The stimulation of angiogenesis by glycated phosphatidylethanolamine was investigated by using cultured cells, food components that can inhibit glycation of phospholipids were screened.Based on these present knowledge, foods and food components that can prevent angiogenic disorders diseases such as cancer, diabetic retinopathy atherosclerosis and arthritis will be effectively developed.

血管生成是产生新的毛细血管的过程，涉及内皮细胞增殖、细胞迁移和毛细血管形成。异常血管生成与诸如癌症、糖尿病视网膜病变、动脉粥样硬化和关节炎的难治性疾病有关。因此，有趣的是，目前抑制血管生成是预防这些疾病的最有吸引力的方法之一。此外，食物和食物成分对血管生成的调节也成为一个重要的问题，我们以前的研究表明，共轭三烯脂肪酸和生育三烯酚比一些药物更有效地抑制血管生成。此外，我们还证实了Amadori糖基化磷脂酰乙醇胺（一种脂质连接的糖基化化合物）作为血管生成的促进剂的存在。本研究中，1）将共轭三烯脂肪酸喂给移植肿瘤细胞的裸鼠，研究共轭三烯脂肪酸的抗肿瘤机制和抗血管生成活性。2)本研究对生育酚的天然类似物生育三烯酚在体内外的抗血管生成机制进行了研究。3)利用培养的细胞研究了糖基化磷脂酰乙醇胺对血管生成的刺激作用，筛选出能抑制磷脂糖基化的食品成分，在此基础上，将有效地开发出能预防肿瘤、糖尿病视网膜病变、动脉粥样硬化、关节炎等血管生成障碍性疾病的食品和食品成分。

项目成果

Tumor growth suppression by a-eleostearic acid, a linolenic acid isomer with a conjugated triene system, via lipid peroxidation.

α-桐油酸（一种具有共轭三烯系统的亚麻酸异构体）通过脂质过氧化抑制肿瘤生长。

• 发表时间: 2004
• 期刊: Carcinogenesis 25
• 作者: T.Tsuzuki;Y.Tokuyama;M.Igarashi;T.Miyazawa
• 通讯作者: T.Miyazawa

Inhibition for neovasculation, cell multiplication, lumen formation and FGF,

抑制新血管形成、细胞增殖、管腔形成和 FGF，

• 发表时间: 2002

DNA chip analysis of comprehensive food function : Inhibition of angiogenesis and telomerase activity with unsaturated vitamin E, tocotrienol.

DNA芯片分析食品综合功能：不饱和维生素E、生育三烯酚抑制血管生成和端粒酶活性。

• 发表时间: 2004
• 期刊: Biofactors. 21
• 作者: K.Nakagawa;T.Eitsuka;H.Inokuchi;T.Miyazawa
• 通讯作者: T.Miyazawa

Amadori-glycated phosphatidylethanolamine induces angiogenic differentiations in cultured human umbilical vein endothelial cells

• DOI: 10.1016/s0014-5793(03)01237-7
• 发表时间: 2003-12-04
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Oak, JH;Nakagawa, K;Miyazawa, T
• 通讯作者: Miyazawa, T

Anti-angiogenic activity of tocotrienol

• DOI: 10.1271/bbb.67.1623
• 发表时间: 2003-07-01
• 期刊: BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
• 影响因子: 1.6
• 作者: Inokuchi, H;Hirokane, H;Miyazawa, T
• 通讯作者: Miyazawa, T