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STUDY ON THE SIGNIFICANCE OF LOX-1 IN OXIDATIVE STRESS-RELATED BIOLOGICAL RESPONSES

LOX-1在氧化应激相关生物反应中的意义研究

基本信息

批准号：
16390070
负责人：
SAWAMURA Tatsuya
金额：
$ 9.47万
依托单位：
National Cardiovascular Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390070/
关键词：
oxidized LDL receptor LOX-1 oxidized LDL endothelial cells arteriosclerosis intimal thickening

项目摘要

We have identified the oxidized LDL receptor expressed in endothelial cells. After the discovery, roles of LOX-1 in oxidative stress-related pathological responses and diseases were suggested. In the present study, we have employed (1) rat model for balloon arterial injury and (2) LOX-1 overexpressing ApoEKO mice to explore the role of LOX-1 in intimal thickening after PTCA and in coronary atherosclerosis.(1) Intima of rat carotid artery was injured by an inflated balloon catheter. The induction of the expression of LOX-1 was detected immediately after the injury by RT-PCR analyses. Immnohistochemistry with anti-LOX-1 antibody showed LOX-1 was localized in imedial smooth muscle cells n the early phase, in intimal smooth muscle cells in intermediate phase, and in regenerated endothelial cells in the late phase. Treatment with anti-LOX-1 antibody reduced the thickening of intima as well as infiltration of leukocytes and oxidative stress.(2) Heart of the LOX-1 overexpressing ApoEKO mice was analyzed, being compared with ApoEKO mice. Deposition of oxidized LDL, oxidative stress, expression of adhesion molecules, infiltration of macrophages, and lipid deposition were increased in LOX-1 overexpressing mice compared with ApoEKO mice.These results suggest that LOX-1 is involved in the pathology of intimal thickening after balloon arterial injury and lipid deposition under hyper lipidemia. In both models oxidative stress are increased and LOX-1,at least in part, enhances the oxidative stress in the lesion. Manipulating LOX-1 activity might be a novel therapeutic approach for in oxidative stress-related diseases including these diseases.

我们已经确定了在内皮细胞中表达的氧化LDL受体。在发现之后，LOX-1在氧化应激相关的病理反应和疾病中的作用被提出。在本研究中，我们使用（1）大鼠球囊动脉损伤模型和（2）LOX-1过表达的ApoEKO小鼠来探讨LOX-1在PTCA后内膜增厚和冠状动脉粥样硬化中的作用。(1)用球囊导管损伤大鼠颈动脉内膜。RT-PCR检测损伤后立即检测LOX-1的表达诱导。LOX-1抗体免疫组化结果显示，LOX-1在早期定位于内膜平滑肌细胞，中期定位于内膜平滑肌细胞，晚期定位于再生内皮细胞。用抗LOX-1抗体治疗减少内膜增厚以及白细胞浸润和氧化应激。(2)分析LOX-1过表达ApoEKO小鼠的心脏，并与ApoEKO小鼠进行比较。与ApoEKO小鼠相比，LOX-1过表达小鼠氧化LDL沉积、氧化应激、粘附分子表达、巨噬细胞浸润和脂质沉积增加，提示LOX-1参与了球囊损伤后内膜增厚和高脂状态下脂质沉积的病理过程。在这两种模型中，氧化应激增加，LOX-1至少部分地增强了病变中的氧化应激。调控LOX-1活性可能成为治疗氧化应激相关疾病的新途径。

项目成果

期刊论文数量（57）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Oxidized low-density lipoprotein (ox-LDL) binding to lectin-like ox-LDL receptor-1 (LOX-1) in cultured bovine articular chondrocytes increases production of intracellular reactive oxygen species (ROS) resulting in the activation of NF-kappaB.

DOI：
发表时间：
2004
期刊：
Osteoarthritis and cartilage
影响因子：
7
作者：
Shunji Nishimura;M. Akagi;Koji Yoshida;S. Hayakawa;T. Sawamura;H. Munakata;C. Hamanishi
通讯作者：
Shunji Nishimura;M. Akagi;Koji Yoshida;S. Hayakawa;T. Sawamura;H. Munakata;C. Hamanishi

Adhesion molecule expression in fibroblasts : alteration in fibroblast biology after transfection with LOX-l plasmids.

成纤维细胞中粘附分子的表达：用LOX-1质粒转染后成纤维细胞生物学的改变。