2001 Fiscal Year Final Research Report Summary
Role of asymmetric dimethylarginine (ADMA) and its hydrolases (DDAH I and II) in atnerogenesis
| Project/Area Number |
12670652
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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 |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOSHIZUMI Masao Department of Geriatric Medicine, The University of Tokyo, Senior Assistant, 医学部・附属病院, 講師 (20282626)
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| Co-Investigator(Kenkyū-buntansha) |
SANTA Tomohumi Department of Bioorganic Chemistry, The University of Tokyo, Associate Professor, 医学部・附属病院, 助教授 (30187306)
IIJIMA Katsuya Department of Geriatric Medicine, The University of Tokyo, Assistant, 医学部・附属病院, 助手 (00334384)
OUCHI Yasuyoshi Department of Geriatric Medicine, The University of Tokyo, Professor, 医学部・附属病院, 教授 (80168864)
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| Project Period (FY) |
2000 – 2001
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| Keywords | arteriosclerosis / vascular endothelial cells / nitric oxide / vasodilatation / neointima / vascular smooth muscle cells / transcription / dedifferentiation |
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| Research Abstract |
The goal of our study is to elucidate the role of Asymmetric NG, NG-dimethylarginine (ADMA) and its hydrolases NG, NG-dimethylarginine dimethylaminohydrolase (DDAH) I and II in the process of arteriosclerosis. Asymmetric NG, NG-dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase, and is known to be elevated in plasma from patients with known cardiovascular risk factors. NG, NG-dimethylarginine dimethylaminohydrolase (DDAH) hydrolyzes ADMA, and there are two isoforms of DDAH I and II reported. It has been reported that NO inhibits intimal thickening. Because plasma concentration of ADMA has not been increased in rat balloon injury model, we hypothesized that a local ADMA/DDAH system may have some roles in the neointima formation. To investigate the role of ADMA in vivo, we have raised polyclonal antibodies against DDAH I and II, and stained thickened intima after balloon injury in rats. In normal carotid artery, endothelial cells and few vascular smooth muscle cells (SMC) in the media were DDAH I and II positive. Two weeks after balloon injury, most of SMC in the neointima were positively stained with DDAH I and II antibody. The expression of DDAH I and II (protein as well as mRNA ), was significantly higher in cultured SMC (de-differentiated state) than in aortic media SMC. DDAH I and II were further upregulated by PDGF-BB (20ng/ml) or serum treatment on cultured SMC, which increased the expression of Smemb. Our results suggest that DDAH in the de-differentiated neointima may have some regulatory effects on the intimal thickening.
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Research Products
(12 results)
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[Publications] lijima K, Yoshizumi M, Hashimoto M, Akishita M, Kim S, Ako J, Liang YQ, Sudoh N, Watanabe T, Ohike Y, Nakahara K, Ouchi Y: "Red Wine Polyphenols Inhibit Vascular Smooth Muscle Cell Migration Through Two Distinct Signaling Pathways"Circulation. in press. (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Watanabe T, Yoshizumi M, Akishita M, Eto M, Toba K, Hashimoto M, Nagano K, Liang YQ, Ohike Y, Iijima K, Sudoh N, Kim S, Nakaoka T, Yamashita N, Ako J, Ouchi Y: "Induction of nuclear orphan receptor NGFI-B gene and apoptosis in rat vascular smooth muscle cells treated with pyrrolidinedithiocarbamate"Arterioscler Thromb Vasc Biol. 21(11). 1738-1744 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Iijima K, Yoshizumi M, Hashimoto M, Kim S, Eto M, Ako J, Liang YQ, Sudoh N, Hosoda K, Nakahara K, Toba K, Ouchi Y: "Red wine polyphenols inhibit proliferation of vascular smooth muscle cells and downregulate expression of cyclin A gene"Circulation. 101(7). 805-811 (2000)
Description
「研究成果報告書概要(欧文)」より
