Contribution of an imbalance between oxidant-antioxidant systems to plaque vulnerability in patients with carotid artery stenosis.
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 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.
Uno
Masaaki
M
Department of Neurosurgery, Graduate School of Health Biosciences, University of Tokushima, Faculty of Pharmaceutical Sciences, Showa University, Tokyo, Japan. muno@clin.med.tokushima-u.ac.jp
Kitazato
Keiko T
KT
Suzue
Atsuhiko
A
Itabe
Hiroyuki
H
Hao
Liu
L
Nagahiro
Shinji
S
D000368:Aged; D000975:Antioxidants / Q000502:physiology*; D016893:Carotid Stenosis / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000503:physiopathology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000378:metabolism*
D000975:Antioxidants; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase