| Project/Area Number |
07671240
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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 |
Kidney internal medicine
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| Research Institution | UNIVERSITY OF TOKYO |
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Principal Investigator |
TAGUCHI Jun-ichi (1996) Department of Medicine, Assistant, 医学部・付属病院, 助手 (30236400)
伊刈 裕二 (1995) 東京大学, 医学部(病), 助手 (70271567)
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| Co-Investigator(Kenkyū-buntansha) |
UMETZU Michio Department of Medicine, 医学部・付属病院, 医員
OHNO Minoru Department of Medicine, Assistant, 医学部・付属病院, 助手 (00185349)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | AGEs / Oxidative stvess / Platelet / balloon injury / aminoguanidine / 血管 |
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| Research Abstract |
Accumulation of advanced glycation end products (AGEs) has been reported in many chronic pathological disease. However, it is still unknown why and how AGEs accumulate in artherosclerotic lesions without hyperglycemia. To address the question, we hypothesized that oxidative stress induced by vascular injury accelerated local formation of AGEs. In rat carotid artery balloon injury model, superoxide production, NADPH and NADH oxidase activity in membrane fraction and lipid peroxides contents were significantly higher in injured carotid ateries compared with arteries at 10th after injury. In cell free system, AGFs were shown to be dramatically formed in only 5 days even under physiological level of albumin and glucose by addition with H202. It was accelerated by the addition of Fe2+. Immunohistochemistry showed that AGEs accumulated in neointima using either a polyclonal anti-AGE antibody or polyclonal anti-pentosidine antibody at day 14. In conclusion, a rapid local AGEs fromation occurred following vessel injury and oxidative stress might have an important role for the accelerated formation of AGEs. Advanced glycation endproducts (AGEs) increased in diabetic patients are considered to work as oxidants which contribute to diabetic complication.
Platelet aggregation induced by ADP or by U46619 was potentiated when platelets were preincubated with AGE-BSA V.S.unmodified BSA control. Time dependent spontaneous superoxide production measured with chemiluminescence intensity was significantly higher in platelets incubated with AGE-BSA than in those with BSA.Co-presence of SOD suppressed chemiluminescence to the basal level in both AGE-BSA and BSA pretreated platelets. These results suggest that AGEs potentiate platelet aggregation through superoxide and prostanoid production, which may be responsible for hypercoagulability in diabetes.
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