| Co-Investigator(Kenkyū-buntansha) |
KOGA Yasutoshi Kurume University, Department of Pediatrics, Professor, 医学部, 教授 (00225400)
UMEI Hidekazu Kurume University, Department of Internal Medicine III, Instructor, 医学部, 助手 (90360289)
菅野 良 久留米大学, 医学部, 助手 (80330819)
服巻 信也 久留米大学, 医学部, 講師 (90248352)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Numerous studies have demonstrated that oxidative stress plays a pivotal rote in the pathogenesis of cardiovascular dieseases. Superoxide anion is formed by univalent reduction of molecular oxygen. Although several enzymes are involved in the generation of superoxide anion, including xanthine oxidase, NADH/NADPH oxidase, lipoxygenase and nitric oxide synthase, one of the largest factories of superoxide anion in vivo is the mitochondrion. In patients with mitochondrial diseases, vascular complications, not only stroke but also coronary artery diseases, are commonly observed in young subjects without risk factors for atherosclerosis. Abnormal mitochondria, which have a defect in substrate utilization in the respiratory chain or of oxidation-phosphorylation coupling, leading to leakage of superoxide anions, are accumulated in the endothelium and vascular smooth muscle cells in mitochondrial diseases. Endothelium-dependent vasodilation was lost at basal level, which was restored by antioxi
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dant ascorbic acid in patients with mitochondrial diseases, suggesting that oxidative stress may be involved in premature cardiovascular diseases and antioxidants may become a therapeutic tool in mitochondrial diseases. Coenzyme Q plays an essential role in the mitochondrial electron-transport chain. Ubiquinol(CoQH2), the reduced form of coenzyme Q, is a lipid-soluble antioxidant. Although CoQH2 supplementation has been shown to have cell protective effects in experimental models, it remains unknown whether endogenous CoQH2 plays a role in the development of atherosclerosis. The aim of this study was to investigate a possible link between CoQH2 and subclincal atherosclerosis in a general population. In apparently healthy subjects, coronary risk factors were evaluated. Endothelial function was estimated by flow-mediated vasodilation of the brachial artery and plaque score of the common carotid artery were assessed by ultrasonography. Plasma levels of CoQH2 were determined by ELISA. Unexpectedly, univariate analyses revealed that CoQH2 was significantly and positively correlated with risk factors of metabolic sydrome, body mass index, triglyceride, mean arterial pressure, and insulin resistance estimated by HOMA. There was a significant positive relationship between CoQH2 and MDA-modified LDL, a marker of oxidative stress. CoQH2 was also inversely correlated with flow-mediated vasodilation and positively correlated with plaque score. Multiple regression analysis composing of classical risk factors revealed that CoQH2 was an independent determinant of flow-mediated vasodilation and plaque score, respectively. Thus, ubiquinol was paradoxically associated with endothelial dysfunction and subclinical atherosclerosis in subjects with metabolic syndrome. Our results suggest that ubiquinol may be compensatory elevated to prevent atherosclerosis. Less
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