Cloning of LDL receptors responding to fluid shear stress

响应流体剪切应力的 LDL 受体克隆

• 批准号: 24650250
• 负责人: YAMAMOTO Kimiko
• 金额: $ 2.5万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24650250/
• 关键词: 流れ剪断応力; LDLコレステロール; 動脈硬化; 血管内皮細胞; 乱流; 完全長cDNAライブラリー; 発現クローニング

LDL receptors, which were related to the onset of atherosclerosis caused vascular diseases such as the myocardial infarction or the cerebral infarction, were cloned. Although the pathological findings, which the atherosclerosis frequently appears on the endothelial cells exposed to turbulent fluid shear stress in the vascular bifurcation, were widely known, the details of the molecular mechanism were not fully apparent. Two kinds of clones that the mRNA and protein expression levels were down-regulated in response to laminar shear stress whereas those expression levels were up-regulated in response to turbulent shear stress were identified in human vascular endothelial cells by using a full-length cDNA library. The immunostaining study was confirmed that these two kinds of protein were expressed in human atherosclerotic lesions. These results indicate that the molecules discovered in this study play an important role in the mechanism of the onset of atherosclerosis.

克隆了与动脉粥样硬化引起的心肌梗死、脑梗死等血管疾病发生相关的LDL受体。动脉粥样硬化经常出现在血管分叉处受湍流剪切应力影响的内皮细胞上，这一病理发现已广为人知，但其分子机制的细节尚不完全清楚。利用全长cDNA文库，在人血管内皮细胞中鉴定出两种mRNA和蛋白表达水平在层流剪切应力下下调而在湍流剪切应力下上调的克隆。免疫染色研究证实这两种蛋白在人动脉粥样硬化病变中均有表达。这些结果表明，本研究发现的分子在动脉粥样硬化的发生机制中起着重要作用。

项目成果

Dynamic cellular mechanotransduction and nano-biomechanics

动态细胞力转导和纳米生物力学

• 发表时间: 2013
• 作者: Ishitobi H;Wakamatsu A;Lui F;Azami T;Hamada M;Matsumoto K;Kataoka H;kobayashi M;Choi K;Nishikawa S-I;Takahashi S;Ema M;K. Yamamoto and J. Ando
• 通讯作者: K. Yamamoto and J. Ando

Chemiluminescence imaging of flow-induced ATP release at caveolae in vascular endothelial cells.

血管内皮细胞小凹处流动诱导的 ATP 释放的化学发光成像。

• 发表时间: 2012
• 作者: 三國貴康;上阪直史;狩野方伸;K. Yamamoto and J. Ando
• 通讯作者: K. Yamamoto and J. Ando

東京大学 大学院医学系研究科 医用生体工学講座 システム生理学

东京大学医学研究科生物医学工学系系统生理学系

Shear-stress-mediated control of vascular functions through endothelial ATP release and P2X4 ion channels.

通过内皮 ATP 释放和 P2X4 离子通道剪切应力介导的血管功能控制。

• 发表时间: 2012
• 作者: 大石久史;勝又斗紀夫;関口有佳里;長崎はるか;ダーシドーハ;依馬正次;工藤 崇;高橋 智;K. Yamamoto and J. Ando
• 通讯作者: K. Yamamoto and J. Ando

Flow detection and calcium signaling in vascular endothelial cells

血管内皮细胞中的血流检测和钙信号传导

• 发表时间: 2013
• 期刊: Cardiovasc. Res
• 作者: 坪山幸太郎;柏木有太郎;林亜矢子;岩崎広英;岡部繁男;J. Ando and K. Yamamoto
• 通讯作者: J. Ando and K. Yamamoto