Molecular pathological studies on physiological function of VEGF in atherosclerotic Vessels

VEGF在动脉粥样硬化血管中生理功能的分子病理学研究

• 批准号: 07670252
• 负责人: NAKAGAWA Kazunori
• 金额: $ 1.34万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670252/
• 关键词: Atheroscrelosis; Endothelial Cell; Angiogenesis; Gene Transfer; Thrombosis; VEGF; 血栓形成

The endothelial function, including the activation and regulation of both procoagulant and anticoagulant properties, has been considered to play a critical role in pathophysiology of blood vessel. To clarify the patho-biological function of endothelial cells, we developed new technique (ex vivo procoagulant activity assay method and HVJ-cationic liposome gene transfer technique) or new animal model (CA-LPS DIC model, etc.) and we performed histochemical, cell biological or genetical analyzes in vivo and in vitro.We revealed that atherosclerotic vessel tended to be a hypercoagulantstate and that vascular endothelial growth factor (VEGF) promoted the intimal thickness and angiogenesis in rabbit atherosclerotic model. We also demonstrated that VEGF play a central role in the modulation of endothelial cell function, especially neovascularization and hyperpermeability of blood vessels in diabetic retinopathy and placental development. Moreover, we examined the availability of antithrombotic agent, a recombinant tissue factor pathway inhibitor in thrombosis model.These results and techniques may provide a new insight for more comprehensive on endothelial function in vessel walls as well as therapeutic implications in vascular diseases.

内皮功能，包括促凝血和抗凝血特性的激活和调节，被认为在血管的病理生理学中发挥着关键作用。为了阐明内皮细胞的病理生物学功能，我们开发了新技术（离体促凝活性测定方法和HVJ-阳离子脂质体基因转移技术）或新的动物模型（CA-LPS DIC模型等），并在体内和体外进行了组织化学、细胞生物学或遗传学分析。 血管内皮生长因子（VEGF）促进兔动脉粥样硬化模型的内膜厚度和血管生成。我们还证明，VEGF 在调节内皮细胞功能，尤其是糖尿病视网膜病变和胎盘发育中的新生血管形成和血管通透性过高方面发挥着核心作用。此外，我们还研究了抗血栓剂（一种重组组织因子途径抑制剂）在血栓形成模型中的可用性。这些结果和技术可能为更全面地了解血管壁内皮功能以及血管疾病的治疗意义提供新的见解。

项目成果

Shiraishi S et al: "The immunohistchemical localization of vascular endothelial growth faotor in human placenta" Placenta. (in press).

Shiraishi S 等人：“人胎盘中血管内皮生长因子的免疫组织化学定位”胎盘。

Nakagawa K et al: "Tissue distribution and subcellular localization of rabbit liver metalloendopeptidase." J Histochem Cytochem. 45(1). 41-47 (1997)

Nakakawa K 等人：“兔肝金属内肽酶的组织分布和亚细胞定位。”

Ichikawa K,Nakagawa K,Hirano K,Sueishi K: "The localization of tissue factor and apolipoprotein (a) in atherosclerotic lesions of the human aorta and their relation to fibrinogen-fibrin transition" Path Res Pract. 192(3). 224-232 (1996)

Ichikawa K、Nakakawa K、Hirano K、Sueishi K：“组织因子和载脂蛋白 (a) 在人类主动脉动脉粥样硬化病变中的定位及其与纤维蛋白原-纤维蛋白转变的关系”Path Res Pract。

Ishibashi H.Nakagawa K.Nakashima Y.Sueishi K.: "Conditioned media of carcinoma cells cultured in hypoxic microenviroment stimulated angiogenesis in vitro : The relationship to basic fibroblast growth factor." Virchows Archiv. 425(6). 561-568 (1995)

Ishibashi H.Nakakawa K.Nakashima Y.Sueishi K.：“在缺氧微环境中培养的癌细胞的条件培养基刺激体外血管生成：与碱性成纤维细胞生长因子的关系。”

Kato K,Elsayd YA,Namoto M,Nakagawa K,Sueishi K: "Enhanced expression of tissue factor activity in the atheroscrelotic aortas choresterol-fed rabbit." Thromb Res. 82(4). 335-347 (1996)

Kato K、Elsayd YA、Namoto M、Nakakawa K、Sueishi K：“动脉粥样硬化主动脉 Choresterol 喂养的兔子中组织因子活性的表达增强。”