Grant-in-Aid for Scientific Research (A)
|Allocation Type||Single-year Grants |
|Research Institution||KYUSHU UNIVERCITY |
SUEISHI Katsuo Kyushu University, Graduate School of Medical Sciences, Professor, 大学院医学研究院, 教授 (70108710)
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)
米満 吉和 九州大学, 大学院・医学研究院, 助教授 (40315065)
|Project Period (FY)
2004 – 2006
Completed (Fiscal Year 2006)
|Budget Amount *help
¥48,100,000 (Direct Cost: ¥37,000,000、Indirect Cost: ¥11,100,000)
Fiscal Year 2006: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2005: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2004: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
|Keywords||vascular remodeling / angiogenesis / arteriogenesis / atherosclerosis / cancer / VEGFs / FGF-2 / SIV / SeV / 血管リモデリング / リンパ管新生 / 血管内(前駆)細胞 / 周皮細胞 / 血管内皮(前駆)細胞 / 周波細胞 / PDGF-A / B|
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.