Object: 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 manganese superoxide dismutase (SOD) and Cu-ZnSOD that catalyze dismutation of oxygen to H2O2. Low-molecular antioxidants such as uric acid regulate the inactivation that appears to be linked to an increase in peroxynitrite resulting in oxidized LDL (OxLDL) elevation. The authors evaluated whether a focal imbalance between pro- and antioxidant systems induces plaque vulnerability in patients with carotid artery (CA) stenosis.
Methods: Carotid artery plaques obtained in 35 patients who had undergone carotid endarterectomy were classified as vulnerable or stable based on histopathological findings. In vulnerable plaques, OxLDL, measured using enzyme-linked immunosorbent assay, 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 eighth of that in plasma and appeared to be unable to protect Cu-ZnSOD from degradation by H2O2. Immunohistochemical analysis showed increased peroxynitrite and OxLDL in vulnerable plaques. There was a significant correlation between plaque and plasma OxLDL levels (p < 0.01).
Conclusions: Analysis of the results suggests that a focal imbalance between pro- and antioxidant defense systems in patients with CA plaques induces an increase in plaque OxLDL levels and consequent plaque instability, contributing to high levels of plasma OxLDL.