2004 Fiscal Year Final Research Report Summary
Imbalance between Oxidant/Antioxidant Systems Contributes to Plaque Vulnerability in Patients with Carotid Stenosis
| Project/Area Number |
15591529
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | The University of Tokushima |
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Principal Investigator |
UNO Masaaki The University of Tokushima, Institute of Health Biosciences, Associate Professor, 大学院・ヘルスバイオサイエンス研究部, 講師 (90232884)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAHIRO Shinji The University of Tokushima, Institute of Health Biosciences, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (60145315)
SUZUE Atsuhiko The University of Tokushima, Institute of Health Biosciences, Assistant, 大学院・ヘルスバイオサイエンス研究部, 助手 (60346608)
ITABE Hiroyuki Showa University, Department of Biological Chemistry, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30203079)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Vulnerable carotid plaque / oxidized LDL / superoxide dismutase |
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| Research Abstract |
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.
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Research Products
(22 results)
