動脈硬化の分子機構

动脉硬化的分子机制

• 批准号: 09281104
• 负责人: KITA Toru
• 金额: $ 165.89万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas (A)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09281104/
• 关键词: Atherosclerosis; Vascular endothelial cell; Vasculogenesis; Angiogenesis; Vascular smooth muscle cell; Phenotypic conversion; Adhesion molecule; Oxidized LDL; 脈管形成; ずり応力; 遺伝子導入

The Grants-in-Aid for Scientific Research on Priority Areas No. 09281104 was issued from 1997 to 2000. During the period, we organized a research group with scientists who are considered to be most active in the research field. Atherosclerosis is correlated with a variety of vascular disorders such as coronary heart disease. We therefore placed our goal on elucidation of the molecular mechanism of atherosclerosis and exploration of novel therapeutic strategies. To conduct investigation, the members were divided into 3 subgroups, i.e. Group 1, 2, and 3 with different subject of study as follows. We also formed a Central Committee to coordinate and facilitate the research activity of the subgroups.[Group 1] Study subject : Molecular mechanism of vascular formation. Atherosclerosis has been considered to evolve according to the mechanism shared with vascular formation in the body. During the research period, we have made a significant progress in understanding vasculogenesis and angiogene … More sis. In Conclusion, the roles of new molecules such as transcription factor ets-1 and other molecules were clarified. [Group 2] Study subject : Endothelial dysfunction and blood cells. There has been accumulating evidence that atherosclerosis is initiated by endothelial dysfunction due to a variety of biological insults. We therefore formed this subgroup to explore the key molecules involved in those events. We discovered novel scavenger receptors such as LOX-1 and SRPSOX. Furthermore, we revealed that adipose tissues produce cytokines abundantly. Among those cytokines, adiponectin has been shown to play an important role in atherogenesis and insulin resistance. [Group 3] Study subject : Molecular mechanism of phenotypical conversion and proliferation of vascular smooth muscle cells. This subgroup focused on the mechanism of phenotypical conversion of vascular smooth muscle cells, which is believed to be the characteristic feature of the advanced atherosclerotic lesions. To clarify these points, a variety of transcription factors such as BTBE2 were examined. Also, the new methods to deliver genes were developed.In conclusion, we have made a successful progress in atherosclerosis research, which will be translated into clinical application in the near future. Less

1997年至2000年发放了第09281104号优先领域科学研究补助金。在此期间，我们组织了一个研究小组，其中包括被认为在研究领域最活跃的科学家。动脉粥样硬化与各种血管疾病如冠心病有关。因此，我们的目标是阐明动脉粥样硬化的分子机制和探索新的治疗策略。为了进行调查，将成员分为3个亚组，即第1、2和3组，研究主题如下。我们还成立了一个中央委员会，以协调和促进各分组的研究活动。[第1组]研究主题：血管形成的分子机制。动脉粥样硬化一直被认为是根据与体内血管形成共有的机制进化的。在研究期间，我们在血管发生和血管生成基因的认识上取得了重大进展 ...更多信息 姐结论阐明了转录因子ets-1等新分子的作用。[第2组]研究对象：内皮功能障碍和血细胞。越来越多的证据表明，动脉粥样硬化是由各种生物损伤引起的内皮功能障碍引起的。因此，我们成立了这个小组来探索参与这些事件的关键分子。我们发现了新的清道夫受体，如LOX-1和SRPSOX。此外，我们发现，脂肪组织产生大量的细胞因子。在这些细胞因子中，脂联素已被证明在动脉粥样硬化和胰岛素抵抗中起重要作用。【第3组】研究课题：血管平滑肌细胞表型转化和增殖的分子机制。该亚组集中于血管平滑肌细胞表型转化的机制，这被认为是晚期动脉粥样硬化病变的特征性特征。为了阐明这些观点，研究了多种转录因子，如BTBE 2。总之，我们在动脉粥样硬化的研究中取得了成功的进展，在不久的将来将转化为临床应用。少

项目成果

Minami, M., Kume, N., et al.: "Expression of SR-PSOX, a novel cell-surface receptor for atherogenic oxidized low density lipoprotein, in human atherosclerotic lesions"Arterioscler.Thromb.Vasc.Biol.. 21. 1796-1800 (2001)

Minami, M., Kume, N. 等人：“SR-PSOX 的表达，一种新型细胞表面致动脉粥样硬化氧化低密度脂蛋白受体，在人动脉粥样硬化病变中的表达”Arterioscler.Thromb.Vasc.Biol.. 21。

Kanaki, T., Bujo, H. et al.: "Expression of LR11, a mosaic LDL receptor family member, is markedly increased in atherosclerotic lesions"Arterioscler. Thromb. Vasc. Biol.. 19. 2687-2695 (1999)

Kanaki, T., Bujo, H. 等人：“LR11（一种嵌合 LDL 受体家族成员）的表达在动脉粥样硬化病变中显着增加”Arterioscler。

Wakiya,K.et al.: "A cyclic AMP response element and an ETS motif are involved in the transcreptional regulation 0 flt-1 tyrosine kinase (VEGF receptor 1) gene." J.Biol.Chem.271. 30823-30828 (1996)

Wakiya,K. 等人：“环状 AMP 反应元件和 ETS 基序参与转录调节 0 flt-1 酪氨酸激酶（VEGF 受体 1）基因。”

Sano, H., Sudo, T., Yokode, M., et al.: "Functional Blockade of Platelet-derived Growth Factor Receptor-β but Not of Receptor-α Prevents Vascular Smooth Muscle Cell Accumulation in the Fibrous Cap Lesions in Apolipoprotein E-deficient Mice"Circulation. 10

Sano, H.、Sudo, T.、Yokode, M. 等人：“功能性阻断血小板衍生生长因子受体-β 但不阻断受体-α 可防止载脂蛋白纤维帽病变中血管平滑肌细胞积聚E-缺陷小鼠”循环。10

Sekiguchi K, Kurabayashi M, et al.: "Homeobox protein hex induces SMemb/Nonmuscle myosin heavy chain-B gene expression through the cAMP-responsive element"Circ Res. 88. 52-58 (2001)

Sekiguchi K、Kurabayashi M 等人：“同源框蛋白 hex 通过 cAMP 响应元件诱导 SMemb/非肌肉肌球蛋白重链 B 基因表达”Circ Res。