2006 Fiscal Year Final Research Report Summary
Moleculo-pathological Study on the Homeostatic and Deregulated Mechanisms of Vascular Remodeling
| Project/Area Number |
16209012
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | KYUSHU UNIVERCITY |
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Principal Investigator |
SUEISHI Katsuo Kyushu University, Graduate School of Medical Sciences, Professor, 大学院医学研究院, 教授 (70108710)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Kazunori Kyushu University, Graduate School of Medical Sciences, Assistant Professor, 大学院医学研究院, 講師 (50217668)
KOGA Takaomi Kyushu University, Hospital, Assistant Professor, 大学病院, 講師 (70380615)
ONIMURA Mitsuho Kyushu University, Graduate School of Medical Sciences, Research Associate, 大学院医学研究院, 助手 (00380626)
OKANO Shinji Kyushu University, Graduate School of Medical Sciences, Research Associate, 大学院医学研究院, 研究員 (10380429)
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| Project Period (FY) |
2004 – 2006
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| Keywords | vascular remodeling / angiogenesis / arteriogenesis / atherosclerosis / cancer / VEGFs / FGF-2 / SIV / SeV |
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| Research Abstract |
Major findings obtained in this project are as follows :
1. Patho-physiological study on the pathological vascular remodeling
1)Atherosclerosis and angiogenesis : Intimal neovascularization related to the function of not only VEGF-A, C and D expression but also PEDF in human coronary arteries and aortas were immunohistochemically examined and clarified to be equivalent to the histopathological hallmark of active atherogenesis, leading to the hypothesis that intimal neovascularization participates intimately in the progression of human atherosclerosis on the basis of "inflammation and repair process".
2)Aortic atherosclerosis in apoE-/-mice was accelerated by VEGF-A and-C through VEGFR-1/2 and-2/3 heteromers, but not through single activation of VEGFR activated by VEGF-B/E and P1GF.
3)Pathologically examining autopsy cases in Hisayama-Cohort Study, diabetes mellitus and chronic renal failure became evident to be an independent risk factor of coronary atherosclerosis.
4)PKC activation and suppression of PDGF-B induced in STZ-induced diabetic animal models intimately corresponded to the both low resistance to tissue ischemia and insufficient angiogenesis/vasculogenesis.
5)The positive interaction between VEGF-C and PDGF-B played an important role in the functional angiogenesis in ischemic tissues, in addition to the Ang-1/Tie-2/PDGF-B interaction. Moreover, FGF-2 function could enhance these positive loops, and thus can actively participate in the integrated angiogenesis.
2. Exploitation of novel gene transfer vectors and their clinical applications
1)Molecular and biological characteristics of SIV, particularly on ubiquitous cell targets and low frequency of insertional mutagenesis have been clarified.
2)FGF-2-dFSeV and PEDG-SIV have been progressed to the clinical researches, namely, to human peripheral arterial disease (atherosclerosis obliterans and Buerger disease) and retinal degeneration, respectively.
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[Journal Article] A nonsynonymous SNP in PRKCH (protein kinase Cη) increases the risk of cerebral infarction.2007
Author(s)
Kubo M, Hata J, Ninomiya T, Matsuda K, Yonemoto K, Nakano T, Matsushita T, Yamazaki K, Ohnishi Y, Saito S, Kitazono T, Ibayashi S, Sueishi K, Iida M, Nakamura Y, Kiyohara Y
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Journal Title
Nature Genetics 39(2)
Pages: 212-217
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Actions of ZD0947, a novel ATP-sensitive K+ channel opener, on membrane currents in human detrusor myocytes.2006
Author(s)
Aishima M, Tomoda T, Yunoki T, Nakano T, Seki N, Yonemitsu Y, Sueishi K, Naito S, Ito Y, Teramoto N
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Journal Title
Br J Pharmacol 149
Pages: 542-550
Description
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[Journal Article] Non-endothelial mesenchymal cell- derived MCP-1 is required for FGF-2-mediated therapeutic neovascularization-critical role of the inflammatory/arteriogenic pathway-.2006
Author(s)
Fujii T, Yonemitsu Y, Onimaru M, Tanii M, Nakano T, Egashira K, Takehara T, Inoue M, Hasegawa M, Kuwano H, Sueishi K
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Journal Title
Arterioscl Thromb Vase Biol 26(11)
Pages: 2483-2489
Description
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[Journal Article] The regulation of vascular endothelial growth factors (VEGF-A,-C, and-D) expression in the retinal pigment epithelium.2006
Author(s)
Ikeda Y, Yonemitsu Y, Onimaru M, Nakano T, Miyazaki M, Kohno R, Nakagawa K, Ueno A, Sueishi K, Ishibashi T
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Journal Title
Exp Eye Res 83(5)
Pages: 1031-1040
Description
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[Journal Article] Induction of efficient antitumor immunity using dendritic cells activated by recombinant Sendai virus and its modulation by exogenous interferon-β gene.2006
Author(s)
Shibata S, Okano S, Yonemitsu Y, Onimaru M, Sata S, Nagata-Takeshita H, Inoue M, Shu T, Hasegawa M, moroi Y, Furue M, Sueishi K
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Journal Title
J Immunol 177(6)
Pages: 3564-3576
Description
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[Journal Article] The ubiquitin-proteasome system plays essential roles in presenting an 8-mer CTL epitope expressed in APC to corresponding CD8+ T cells.2006
Author(s)
Duan X, Hisaeda H, Shen J, Tu L, Imai T, Chou B, Murata S, Chiba T, Tanaka K, Fehling HJ, Koga T, Sueishi K, Himeno K
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Journal Title
Int Immunol 18(5)
Pages: 679-687
Description
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[Journal Article] Diabetic microangiopathy in ischemic limb is a disease of disturbance of the PDGF-BB/PKC axis, but not of impaired expression of angiogenic factors.2006
Author(s)
Tanii M, Yonemitsu Y, Fujii T, Shikada Y, Kohno R, Onimaru M, Okano S, Inoue M, Hasegawa M, Onohara T, Maehara Y, Sueishi K
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Journal Title
Circ Res 98(1)
Pages: 55-62
Description
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