Evaluation of the role of dihydrobiopterin in the regulation of endothelial function in the normal and pathological states
| Project/Area Number |
24590324
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
NOGUCHI Katsuhiko 琉球大学, 医学(系)研究科(研究院), 准教授 (70156181)
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| Co-Investigator(Kenkyū-buntansha) |
TSUTSUI Masato 琉球大学, 大学院医学研究科, 教授 (70309962)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 心血管 / 一酸化窒素 / 血管内皮細胞機能 / 酸化ストレス / 動脈硬化 / ジヒドロビオプテリン / テトラヒドロビオプテリン / dihydrofolate reductase / 血管内皮機能 / 一酸化窒素合成酵素 |
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| Outline of Final Research Achievements |
An elevation of oxidized forms of tetrahydrobiopterin (BH4), especially dihydrobiopterin (BH2), has been reported in the setting of oxidative stress, such as atherosclerotic disorders, where endothelial nitric oxide synthase (eNOS) is dysfunctional, but the role of BH2 in the regulation of endothelial function in vivo remains to be clarified. This study was conducted to evaluate the effect of pharmacologically increased levels of BH2 on development of atherosclerotic lesion using a mouse arteriosclerotic model. Two-week treatment with sepiapterin and methotrexate increased aortic levels of BH2 doubly, but exacerbation of atherosclerotic lesion was not clearly found probably because of unspecific drug actions. Thus, to clarify the role of dihydrofolate reductase (DHFR), an enzyme catalyzing intracellular conversion of BH2 to BH4, in the regulation of endothelial function in vivo, we have been generating a novel mouse model with endothelial cell-specific deletion of DHFR gene.
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] Caffeine Contained in a Cup of Coffee Enhances Microvascular Endothelial Function in Healthy Subjects.2015
Author(s)
Noguchi K, Matsuzaki T, Sakanashi M, Hamadate N, Uchida T, Kina-Tanada M, Kubota H, Nakasone J, Sakanashi M, Ueda S, Masuzaki H, Ishiuchi S, Ohya Y, Tsutsui M
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Journal Title
J Pharmacol Sci
Volume: 127
Issue: 2
Pages: 217-222
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Development of an experimentally useful model of acute myocardial infarction: 2/3 nephrectomized triple nitric oxide synthases-deficient mouse.2014
Author(s)
Uchida T, Furuno Y, Tanimoto A, Toyohira Y, Arakaki K, Kina-Tanada M, Kubota H, Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Igarashi T, Ueno S, Matsushita M, Ishiuchi S, Masuzaki H, Ohya Y, Yanagihara N, Shimokawa H, Otsuji Y, Tamura M, Tsutsui M.
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Journal Title
J Mol Cell Cardiol.
Volume: 77
Pages: 29-41
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Long-Term Treatment With San’o-Shashin-To, a Kampo Medicine, Markedly Ameliorates Cardiac Ischemia-Reperfusion Injury in Ovariectomized Rats via the Redox-Dependent Mechanism2013
Author(s)
Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Sakanashi M, Uchida T, Kina-Tanada M, Kubota H, Arakaki K, Tanimoto A, Yanagihara N, Sakanashi M, Ohya Y, Masuzaki H, Ishiuchi S, Sugahara K, Tsutsui M
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Journal Title
Circulation Journal
Volume: 77
Issue: 7
Pages: 1827-1837
DOI
NAID
ISSN
1346-9843, 1347-4820
Related Report
Peer Reviewed
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