Development of intracellular therapy to induce a regression of coronary arteriosclerotic lesions

开发诱导冠状动脉硬化病变消退的细胞内疗法

• 批准号: 10357006
• 负责人: TAKESHITA Akira
• 金额: $ 23.42万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10357006/
• 关键词: arteriosclerossis; coronary artery; ischemic heart disease; Rho-kinase; signal transduction; coronary vasospasm; regression; サイトカイン; 冠攣縮; Rhoーkinase; 動脈硬化の退縮; arteriosclerossis; coronary artery; ischemic heart disease; Rho-kinase; signal transduction; coronary vasospasm; regression; サイトカイン; 冠攣縮; Rhoーkinase; 動脈硬化の退縮

1. In the porcine femoral arteries injured by balloon technique, Rho-kinase was upregulated both at the mRNA and activity levels. The in vivo gene transfer of dominant-negative Rho-kinase (DNRhoK) significantly inhibited the development of the balloon injury-induced vascular lesions.2. The long-term treatment of the porcine coronary artery from the adventitial with MCP-1 and Ox-LDL caused a development of arteriosclerotic lesions (intimal thickening and geometric remodeling). The long-term blockade of Rho-kinase with hydroxyfasudil significantly suppressed the development of those vascular lesions.3. The long-term treatment of the porcine coronary artery from the adventitial with IL-1β caused a development of arteriosclerotic lesions (intimal thickening and geometric remodeling). The long-term blockade of Rho-kinase with hydroxy fasudil caused a regression of those vascular lesions in vivo.4. The in vivo gene transfer of DNRhoK induced a regression of constrictive remo deling in a porcine model with IL-1b/These results indicate that Rho-kinase is substantially involved in the pathog enesis of coronary arteriosclerosis and that the long-term inhibition of the molecule could induce a regression of the arterioclerotic vascular lesions.

1。在球囊技术受伤的猪股动脉中，Rho-kinase在mRNA和活性水平上进行了更新。主体基因转移显性阴性Rho-激酶（DNRHOK）显着抑制了球囊损伤引起的血管病变的发展。2。用MCP-1和OX-LDL对猪冠状动脉进行的长期治疗引起了动脉硬化病变（内膜增厚）和几何重塑）。与羟基糖酶对Rho-kinase的长期封锁显着抑制了这些血管病变的发展。3。与IL-1β晚期对猪冠状动脉的长期治疗导致动脉粥样硬化病变的发展（内膜增厚和几何重塑）。羟基酶的长期阻断羟基酶与羟基法曲尔导致体内这些血管病变的回归4。 Dnrhok的体内基因转移在具有IL-1B/的猪模型中引起了狭窄的Remo探测的回归，这些结果表明，Rho-激酶基本上与冠状动脉粥样硬化病原体有关，并且分子的长期抑制作用可以诱导对疗效的综合性菌丝的回归。