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

目的：活性氧和氮介导低密度脂蛋白（LDL）的氧化修饰。LDL的氧化被内源性自由基清除酶如MnSOD和Cu-ZnSOD所抑制，它们催化O_2^-歧化为H_2O_2。低分子抗氧化剂如尿酸调节失活，这似乎与导致OxLDL升高的过氧亚硝酸盐增加有关。我们评估是否局灶性的不平衡亲和抗氧化系统诱导斑块的脆弱性患者颈动脉stenosis.Methods和Results：颈动脉斑块从35例接受颈动脉内膜切除术被归类为脆弱或稳定的基础上，组织病理学结果。在易损斑块中，用双抗体夹心ELISA法测定的OxLDL显著高于稳定斑块（p<0.01），而SOD活性显著低于稳定斑块（p<0.05）。斑块及血浆OxLDL水平与斑块SOD活性呈负相关（p<0.01）。所有菌斑中的尿酸水平为血浆尿酸水平的1/4 ~ 1/8，且似乎不能保护Cu-ZnSOD免受H_2O_2的降解。免疫组化方法显示易损斑块中过氧亚硝酸盐和OxLDL增加。结论：颈动脉斑块患者的抗氧化防御系统和促氧化防御系统的局部失衡导致斑块内氧化低密度脂蛋白水平升高，导致斑块不稳定，并导致血浆氧化低密度脂蛋白水平升高。

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.