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Generation of plasma oxidized LDL in the early stages of atherogenesis

动脉粥样硬化早期血浆氧化低密度脂蛋白的产生

基本信息

批准号：
21590073
负责人：
ITABE Hiroyuki
金额：
$ 2.91万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590073/
关键词：
動脈硬化症酸化ストレス酸化LDL ペルオキシレドキシン血管平滑筋 apoE-ノックアウトマウス生体内酸化LDL apoEノックアウトマウスリピドミクス血管平滑筋細胞プロテオミクスリポタンパク質トランスジェリン LPP 酸化ホスファチジルコリンアクロレイン apoB

项目摘要

Deposition of lipid peroxidation products was found in intimal and medial regions in aortas of apoE-knockout mice at 10 week old in which very little atherosclerotic lesion was formed. The protein profiles of the two aortic tissues, aortic origin and aortic arch which are prone to atherosclerotic lesion formation, and thoracic and abdominal aortas which form atherosclerotic lesions much later, were examined. We found that peroxiredoxin 2(Prx2), an anti-oxidative stress enzyme, and SM22, a marker for smooth muscle cell differentiation, were reduced expressions in the athero-prone tissues, suggesting a possibility that athero-prone tissue reduces its anti-oxidative stress potential and increase smooth muscle differentiation status. In aortic origin, Prx2 expression was high at 4 weeks of age and lower at 10 and 20 weeks of age. At sites of medial layer with high expression of Prx2, migration of macrophages into adjacent intima was scarcely observed. When a few macrophages are present in intima, the adjacent medial tissue has very low expression of Prx2. It is possible that transmigration of macrophages into intima may be facilitated by reduction of medial Prx2 expression. In the lesions with intimal thickening with a number of accumulated macrophages Prx2 expression increased in both medial and intimal tissues. Accumulation of inflammatory cells in intima could enhance Prx2 expression in media. From these observations, in the very early stages of atherogenesis in mouse aortas, decrease in anti-oxidative enzyme Prx2 expression could increase oxidative stress in the tissues and induce lipid peroxidation. Such a temporal change would be important event as a trigger of the early steps of atherogenesis.

在10周大的apoe基因敲除小鼠主动脉的内膜和内侧区域发现脂质过氧化产物沉积，其中很少形成动脉粥样硬化病变。检测了易形成动脉粥样硬化病变的主动脉弓和主动脉弓组织以及较晚形成动脉粥样硬化病变的胸主动脉和腹主动脉的蛋白谱。我们发现抗氧化应激酶过氧化物还蛋白2（Prx2）和平滑肌细胞分化标志物SM22在动脉粥样硬化易发组织中的表达减少，提示动脉粥样硬化易发组织可能降低其抗氧化应激潜能，增加平滑肌分化状态。在主动脉原点，Prx2的表达在4周龄时高，在10周龄和20周龄时低。在Prx2高表达的内层部位，几乎没有巨噬细胞向邻近内膜迁移。当少量巨噬细胞存在于内膜时，邻近的内侧组织Prx2表达极低。巨噬细胞向内膜的迁移可能是通过减少内侧Prx2的表达来促进的。在巨噬细胞大量积聚的内膜增厚病变中，Prx2在内侧和内膜组织中的表达均升高。炎症细胞在内膜内的积聚可增强介质中Prx2的表达。由此可见，在小鼠主动脉动脉粥样硬化的早期阶段，抗氧化酶Prx2表达降低可增加组织氧化应激，诱导脂质过氧化。这样的时间变化将是一个重要的事件，作为触发动脉粥样硬化的早期步骤。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Behavior of oxidized LDL in plasma and in arterilal tissue during atherosclerosis

动脉粥样硬化期间血浆和动脉组织中氧化低密度脂蛋白的行为

DOI：
发表时间：
2009
期刊：
影响因子：
0
作者：
Iwasa;T.;Takahashi;R.;Nagata;K.;and Kobayashi;Y.;Tomoyuki Kaneiwa;齋藤康昭;H. Itabe
通讯作者：
H. Itabe

Transient Increase in Plasma Oxidized LDL During the Progression of Atherosclerosis in Apolipoprotein E Knockout Mice

DOI：
10.1161/atvbaha.108.164723
发表时间：
2009-01-01
期刊：
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
影响因子：
8.7
作者：
Kato, Rina;Mori, Chihiro;Itabe, Hiroyuki
通讯作者：
Itabe, Hiroyuki

動脈硬化の初期病変と酸化ストレス

动脉硬化和氧化应激的早期病变

DOI：
发表时间：
2012
期刊：
影响因子：
0
作者：
Funakoshi-Tago M;Tago K;Sumi K;Abe M;Aizu-Yokota E;Oshio T;Sonoda Y;Kasahara T.;加藤里奈
通讯作者：
加藤里奈

Immunohistochemical detection of 13(R)-hydroxyoctadecadienoic acid in atherosclerotic plaques of human carotid arteries using a novel specific antibody.

DOI：
10.1267/ahc.09022
发表时间：
2009-12-29
期刊：
Acta histochemica et cytochemica
影响因子：
2.4
作者：
Shibata N;Toi S;Shibata T;Uchida K;Itabe H;Sawada T;Kawamata T;Okada Y;Uchiyama S;Kobayashi M
通讯作者：
Kobayashi M

HIV-1 Vpr induces TLR4/MyD88-mediated IL-6 production and reactivates viral production from latency