Molecular Pathology of Endothelial Function in the Regulation of Vascular Response to Injuries

血管损伤反应调节中内皮功能的分子病理学

• 批准号: 06454186
• 负责人: SUEISHI Katsuo
• 金额: $ 4.74万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 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-06454186/
• 关键词: Endothelial cells; Smooth muscle cells; Macrophages; Athero-and arteriosclerpsis; Thrombosis; Angiogensis; Vascular endothelial growth facator; Gene transfer; 動脈内膜障害・修復; サイトカイン; HVJ・リポゾーム; ヒトCMV・IE遺伝子; 接着蛋白; VEGF

The major results obtained in the final research project year are as follows.1.Atherosclerosis and angiogenesis : The extent of neovascularization in atherosclerotic intima of human coronary arteries correlated well with the luminal stenosis, and this angiogenesis was rich in active atherosclerotic lesions. In addition, the transduction of human VEGF gene into rabbit carotid arteries, using HVJ-liposome as a vector, induced angiomatoid proliferation of endothelial cells, which derived from either adventitial blood vessels or luminal surface, in the fibrocellularly thickened intimas.The angiogeinc mechanism : The angiogenesis via a VEGF-flt receptor interaction playd an important role in the fetal and perinatal development and maturation of placentas and retinas. The intracellular signal transduction was mediated mainly by AP-1 function under the hypoxic conditions.3.The improvement of vascular gene transfer in vivo : We could improve the transfer efficiency of genes of oligonucleotides by HVJ-cationic liposomes instead of HVJ-liposomes. We are also checking the gene transduction routes, efficiency and gene expression by a HVJ-cationic liposome method in liver and airways, comparing with those by a HVJ-liposome method.

最终研究项目年度取得的主要成果如下：1。动脉粥样硬化与血管生成：人冠状动脉粥样硬化内膜新生血管的形成程度与管腔狭窄程度密切相关，且血管生成中存在丰富的动脉粥样硬化活动性病变。此外，以hvj脂质体为载体，将人VEGF基因转导到兔颈动脉中，诱导纤维细胞增厚的内膜中内皮细胞的血管瘤样增殖，内皮细胞来源于外血管或管腔表面。血管生成机制：血管生成通过VEGF-flt受体相互作用在胎儿和围产期胎盘和视网膜发育成熟中起重要作用。缺氧条件下细胞内信号转导主要由AP-1功能介导。血管基因在体内转移的改善：用hvj -阳离子脂质体代替hvj -脂质体可以提高寡核苷酸基因的转移效率。我们还比较了hvj -阳离子脂质体法和hvj -脂质体法在肝脏和气道中的基因转导途径、效率和基因表达。

项目成果

Yoshikazu Yonemitsu: "In situ detection of frequent and active infection of human cytomegalovirus in inflammatory abdominal aortic aneurysms-possible pathogenic role in sustained chronic inflammatory reaction-." Lab Invest. (in press).

Yoshikazu Yonemitsu：“原位检测炎症性腹主动脉瘤中人类巨细胞病毒的频繁和活跃感染——可能在持续慢性炎症反应中发挥致病作用。”

居石克夫: "播種性血管内凝固症候群" 中山書店, 327-344 (1994)

饭石克男：《弥散性血管内凝血》中山书店，327-344（1994）

Minoru Takeuchi: "The localization of lipopolysaccharide in an endotoxemic rat liver and its relation to sinusoidal thrombogenesis." Path Res Pract. 190. 1123-1133 (1994)

Minoru Takeuchi：“内毒素血症大鼠肝脏中脂多糖的定位及其与血窦血栓形成的关系。”

Katsuo Sueishi: "Procoagulant properities of atherosclerotic aortas." The New York Academy of Sciences (in press),

Katsuo Sueishi：“动脉粥样硬化主动脉的促凝血特性。”

Yoshikazu Yonemitsu: "In situ detection of frequent and active infection of human cytomegalovirus in inflammatory abdominal aortic aneurysms." Lab Invest. (in press).

Yoshikazu Yonemitsu：“原位检测炎症性腹主动脉瘤中人类巨细胞病毒的频繁和活跃感染。”