Study on roles of a novel NADPH oxidase isoform in the development of idiopathic pulmonary arterial hypertention

新型 NADPH 氧化酶亚型在特发性肺动脉高压发生中的作用研究

• 批准号: 20590256
• 负责人: IWATA Kazumi
• 金额: $ 3.16万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590256/
• 关键词: 原発性肺高血圧症; 活性酸素; NADPH oxidase; 活性酸素種; NOX1; 遺伝子欠損マウス; 肺動脈平滑筋細胞

Pulmonary arterial hypertension is characterized by hypertrophy of small pulmonary arteries, which leads to right ventricular (RV) hypertrophy and heart failure. Nox1 is a catalytic subunit of NADPH oxidase known as a major source of superoxide production in vascular tissues. In Nox1-defcient mice (Nox1-/Y) hypertrophy of small pulmonary arteries and RV wall were observed. A significant decrease in number of apoptotic cells were demonstrated in pulmonary arterial smooth muscle cells (PASMC) isolated from Nox1-/Y. Dysfunction of Kv1.5, a voltage-dependent potassium channel, is one of the features reported in human and experimental PAH. A significant decrease in Kv1.5 protein and an increase in intracellular potassium levels were observed in Nox1-/Y PASMC.These results suggest that Nox1 plays a critical role in apoptosis of PASMC by regulating Kv1.5 expression and intracellular potassium levels.

肺动脉高压是以小肺动脉肥大为特征，导致右室肥厚和心力衰竭。Nox1是NADPH氧化酶的一个催化亚基，被认为是血管组织中产生超氧化物的主要来源。NOX1基因缺陷小鼠(NOX1-/Y)可见肺小动脉和右室壁肥大。从NOX1-/Y分离的PASMC的凋亡细胞数显著减少。电压依赖性钾通道Kv1.5的功能障碍是人和实验性PAH的特征之一。Nox1-/Y PASMC中Kv1.5蛋白表达显著降低，细胞内钾离子浓度升高。这些结果表明，Nox1通过调节Kv1.5蛋白表达和细胞内钾离子水平在PASMC的凋亡中发挥重要作用。

项目成果

NADPH Oxidase Isoforms and Anti-hypertensive Effects of Atorvastatin Demonstrated in Two Animal Models

• DOI: 10.1254/jphs.09148fp
• 发表时间: 2009-11-01
• 期刊: JOURNAL OF PHARMACOLOGICAL SCIENCES
• 影响因子: 3.5
• 作者: Cui, Wenhao;Matsuno, Kuniharu;Yabe-Nishimura, Chihiro
• 通讯作者: Yabe-Nishimura, Chihiro

原発性肺高血圧症発症にNOX1/NADPH oxidaseが関与する

NOX1/NADPH 氧化酶参与原发性肺动脉高压的发生

• 发表时间: 2009
• 作者: 岩田和実;松野邦晴;矢部千尋
• 通讯作者: 矢部千尋

The AP-1 site is essential for the promoter activity of NOX1/NADPH oxidase, a vascular superoxide-producing enzyme: Possible involvement of the ERK1/2-JunB pathway

• DOI: 10.1016/j.bbrc.2008.07.027
• 发表时间: 2008-09-19
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Cevik, Muhammer Ozgur;Katsuyama, Masato;Yabe-Nishimura, Chihiro
• 通讯作者: Yabe-Nishimura, Chihiro

NOX1/NADPH oxidaseの関わる肺高血圧症の病態分子機構

NOX1/NADPH氧化酶参与肺动脉高压的病理分子机制

• 发表时间: 2010
• 作者: 伊神香菜子;岩田和実;松野邦晴;矢部千尋
• 通讯作者: 矢部千尋

活性酸素産生酵素NADPHオキシダーゼの関わる疾患と病態

与活性氧产生酶NADPH氧化酶相关的疾病和病理状况

• 发表时间: 2009
• 作者: 矢部千尋;松野邦晴;衣斐督和;岩田和実
• 通讯作者: 岩田和実