| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Kazunori KYUSHU UNIVERSITY Faculty of Medicine, Lecturer, 大学院・医学研究院, 講師 (50217668)
NAKASHIMA Yutaka KYUSHU UNIVERSITY Faculty of Medicine, Ass. Prof., 大学院・医学研究院, 助教授 (50135349)
KANEDA Yasufumi KYUSHU UNIVERSITY Osaka Univ., Faculty of Medicine, Prof., 大学院・医学系研究科, 教授 (10177537)
KOMORI Kimihiro KYUSHU UNIVERSITY Faculty of Medicine, Lecturer, 医学部・附属病院, 講師 (40225587)
YONEMITSU Yoshikazu KYUSHU UNIVERSITY Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (40315065)
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| Budget Amount *help |
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Research Abstract |
The major results obtained in the last year (from Apr., 2000 to Mar., 2001) were as follows : 1. Investigation on biological properties of Sendai virus vector (SeV) : 1) the in vitro and in vivo efficiencies of transduction and expression of beta-gal., luciferase, ecNOS, VEGF, FGF-2 and other genes using SeV were almost the same as those by Adeno virus vector, and SeV-mediated gene transfer was characterized by the fact that its brief exposure to cells in vitro and in vivo, less than 10 min., was enough for the peak gene expression. 2) Intaluminal injection of reporter gene-SeV could label not only ECs but also medial SMCs, but the neointima ocurred in human varicose veins hampered the transfection of medial SMCs.
2. In order to confirm the safety of SeV, we examined not only the systemic distribution of reporter genes and sendai virus genom but also the degree of inflammatory reaction including serum/plasma levels of such cytokines as IL-1, 6, 8, TNF-alpha and others. We are now prepar
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ing the format of "Therapeutical application of FGF-2 gene injection to patients with critical limb ischemia using SeV" for getting the approval in the "Ethical Committee of Graduate School of medical Sciences, Kyushu University.
3. Molecular mechanism of angiogenesis in ischemic tissues : 1) Effect of intramuscular injection of VEGF and FGF-2 genes-SeV on development of collateral vessels in ischemic limb mouse model : injection of FGF-2 gene could induce endogeneous VEGF overexpression, and markedly improve blood perfusion in the ischemic limb by enhanced angiogenesis. However, VEGF gene injection worsened blood perfusion in ischemic limb. 2) the final and target angiogenic molecule for accelerating the development of collateral vessels in ischemic tissues was VEGF, but the harmonized collaboration of other angiogenic factors including FGF-2 was necessary for developing effective collateral circulation.
4. In rat pulmonary hypertension induced by monocrotaline, interstitial remodeling by function of infiltrating macrophages through MCP-1 was revealed to be most important in development of pulmonary hypertension, and intra- muscular infection of 7ND MCP-1 gene was effective for its prevention.
5. Pigmentary retinopathy was revealed to be an angiogenic disease by the development of animal models of retroretinal angiogenesis by overexpression of VEGF using SeV. Less
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