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

目的：氧和氮的活性物质介导低密度脂蛋白（LDL）的氧化修饰。内源性自由基清除酶如MnSOD和Cu-ZnSOD可催化O_2^-转化为H_2O_2，从而抑制LDL的氧化。低分子抗氧化剂，如尿酸调节失活，这似乎与过氧亚硝酸盐的增加有关，导致OxLDL升高。我们评估了促氧化系统和抗氧化系统之间的局灶性失衡是否会诱导颈动脉狭窄患者的斑块易损。方法和结果：35例颈动脉内膜切除术患者的颈动脉斑块根据组织病理学结果分为易损斑块和稳定斑块。夹心ELISA检测易损斑块中OxLDL水平显著高于稳定斑块（p<0.01）， SOD活性显著低于稳定斑块（p<0.05）。斑块和血浆OxLDL水平与斑块SOD活性呈负相关（p<0.01）。所有斑块中的生理尿酸水平是血浆中的四分之一到八分之一，似乎无法保护Cu-ZnSOD免受H_2O_2的降解。免疫组织化学方法显示易损斑块中过氧亚硝酸盐和OxLDL增加。斑块与血浆OxLDL水平有显著相关性（p<0.01）。结论：我们的研究结果表明，颈动脉斑块患者的促氧化防御系统和抗氧化防御系统之间的局灶性失衡导致斑块OxLDL水平升高，从而导致斑块不稳定，并导致血浆OxLDL水平升高。

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.