Imbalance between Oxidant/Antioxidant Systems Contributes to Plaque Vulnerability in Patients with Carotid Stenosis

氧化/抗氧化系统之间的不平衡导致颈动脉狭窄患者的斑块脆弱性

• 批准号: 15591529
• 负责人: UNO Masaaki
• 金额: $ 1.92万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591529/
• 关键词: Vulnerable carotid plaque; oxidized LDL; superoxide dismutase; oxidized LDL; Antioxidant; Carotid plaque

Objective : Reactive species of oxygen and nitrogen mediate the oxidative modification of low-density lipoprotein (LDL). Oxidation of LDL is inhibited by endogenous radical scavenging enzymes such as MnSOD and Cu-ZnSOD that catalyze dismutation of O_2^- to H_2O_2. Low molecular antioxidants such as uric acid regulate the inactivation that appears to linked to an increase in peroxynitrite resulting in OxLDL elevation. We evaluated whether a focal imbalance between pro- and antioxidant systems induces plaque vulnerability in patients with carotid stenosis.Methods and Results : Carotid plaques from 35 patients who underwent carotid endarterectomy were classified as vulnerable or stable based on histopathological findings. In vulnerable plaques, OxLDL, measured by sandwich ELISA, was significantly higher (p<0.01) and SOD activity significantly lower than in stable plaques (p<0.05). The plaque and plasma OxLDL levels were inversely correlated with plaque SOD activity (p<0.01). The physiological uric acid level in all plaques was one-fourth to one-eight of that in plasma and appeared to be unable to protect Cu-ZnSOD from degradation by H_2O_2. Immunohistochemical methods disclosed increased peroxynitrite and OxLDL in vulnerable plaques. There was a significant correlation between plaque and plasma OxLDL levels (p<0.01).Conclusion : Our results suggest that a focal imbalance between pro- and antioxidant defense systems in patients with carotid plaques induces an increase in plaque OxLDL levels and consequent plaque instability, and contributes to high levels of plasma OxLDL.

目的：氧和氮的活性物种介导低密度脂蛋白(LDL)的氧化修饰。低密度脂蛋白的氧化受到内源性自由基清除酶的抑制，如催化O_2~-向H_2O_2歧化的锰超氧化物歧化酶和铜-锌超氧化物歧化酶。低分子抗氧化剂如尿酸调节失活，这似乎与过氧亚硝酸根增加导致氧化低密度脂蛋白升高有关。我们评估了前系统和抗氧化系统之间的局部失衡是否导致颈动脉狭窄患者的斑块易损性。方法和结果：35名接受颈动脉内膜切除术的患者的颈动脉斑块根据组织病理学结果被归类为脆弱或稳定。在易损斑块中，夹心ELISA法测得的OxLDL显著高于稳定斑块(p&lt；0.01)，而超氧化物歧化酶活性显著低于稳定斑块(p&lt；0.05)。斑块和血浆OxLDL水平与斑块超氧化物歧化酶活性呈负相关(p&lt；0.01)。所有斑块中的生理性尿酸水平是血浆尿酸水平的四分之一到八分之一，似乎不能保护铜锌超氧化物歧化酶免受H_2O_2的降解。免疫组织化学方法显示，易损斑块中的过氧亚硝酸盐和氧化低密度脂蛋白增加。斑块与血浆Ox低密度脂蛋白水平显著相关(p&lt；0.01)。结论：我们的结果提示颈动脉斑块患者前向防御系统和抗氧化防御系统之间的局部失衡导致斑块OxLDL水平升高，进而导致斑块不稳定，从而导致血浆OxLDL水平升高。

项目成果

Measurement of oxidized LDL present in human plasma and atherosclerotic lesions.

测量人血浆和动脉粥样硬化病变中存在的氧化低密度脂蛋白。

• 发表时间: 2004
• 期刊: International Congress Series 1262
• 作者: Murase N;Rothwell JC;Kaji R;et al.;Itabe H
• 通讯作者: Itabe H

Comparison of FAIR technique with different inversion times and post contrast dynamic perfusion MRI in chronic occlusive cerebrovascular disease.

不同反转时间FAIR技术与对比后动态灌注MRI在慢性闭塞性脑血管病中的比较

• 发表时间: 2003
• 期刊: Magn Reson Imaging 21
• 作者: Hino K;Kurita H;Shiokawa Y;Mohammad A.Jamous;Masaaki Uno;Yoneda K
• 通讯作者: Yoneda K

Does multimodality therapy of arteriovenous malformations improve the patients outcome?

动静脉畸形的多学科治疗能否改善患者的预后？

• 发表时间: 2004
• 期刊: Neurol Res. 26
• 作者: Uno M

Detection of enlarged cortical vein by magnetic resonance imaging contributes to early diagnosis and better outcome for patients with anterior cranial fossa dural arteriovenous fistula.

通过磁共振成像检测扩大的皮质静脉有助于前颅窝硬脑膜动静脉瘘患者的早期诊断和更好的预后。

• 发表时间: 2004
• 期刊: Neurol Med Chir(Tokyo) 44
• 作者: Hino K;Kurita H;Shiokawa Y;Mohammad A.Jamous
• 通讯作者: Mohammad A.Jamous

Raised plasma oxidised LDL in acute cerebral infarction

• DOI: 10.1136/jnnp.74.3.312
• 发表时间: 2003-03-01
• 期刊: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
• 影响因子: 11
• 作者: Uno, M;Kitazato, KT;Nagahiro, S
• 通讯作者: Nagahiro, S