| Project/Area Number |
16390221
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Nagoya University |
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Principal Investigator |
MUROHARA Toyoaki Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (90299503)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Takahisa Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (00303644)
NUMAGUCHI Yasushi Nagoya University, School of Medicine, Associate Professor, 医学部, 助教授 (90378224)
KOMORI Kimihiro Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40225587)
SHIBUYA Masafumi University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (10107427)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | Therapeutic angiogenesis / Vascular regeneration / Regenerative medicine / Gene therapy / Growth factor / Bone marrow cells / Stem cells / Endothelial progenitor cells / 血管再生 / 血管成長因子 / 再生医療 / 虚血性心疾患 / 血管透過性 / 炎症反応 |
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| Research Abstract |
Background
Vascular endothelial growth factor-A (VEGF-A) promotes angiogenesis but causes adverse side effects such as edema or tissue inflammation. VEGF-E, found in the genome of the Orf virus, specifically binds to VEGF receptor-2 and shows mitotic activity on endothelial cells. Recently, we created two forms of VEGF-E and human placental growth factor (P1GF) chimera genes (VEGF-E chimera #9 and VEGF-E chimera #33), which are humanized genes holding VEGF-E function but less antigenicity.
Methods and Results
We examined potential proangiogenic activities of these chimera genes. Four types of expression plasmids (pCDNA3.1-LacZ, phVEGF-A, pVEGF-Echimera#9 and pVEGF-Echimera#33, n=8 each) were administered in a rat model of hindlimb ischemia. Either pVEGF-E chimera #9, pVEGF-E chimera #33 or phVEGF-A significantly increased the ratio of ischemic/normal hindlimb blood-flow compared to the control pCDNA3.1-LacZ treated group. Histochemical staining by alkaline phosphatase also revealed that either pVEGF-Echimera#9, pVEGF-Echimera#33 or phVEGF-A increased the capillary density compared to the pCDNA3.1-LacZ treated group. Furthermore, immunostaining for anti-ED1 revealed that lower number of macrophages were infiltrated in both pVEGF-Echimera#9 and pVEGF-Echimera#33 groups compared to the phVEGF-A group.
Conclusions
Novel VEGF-E/human P1GF chimera genes, pVEGF-Echimera#9 and pVEGF-Echimera#33, significantly stimulated angiogenesis in response to tissue ischemia, whose extent was almost identical to that induced by phVEGF-A with less tissue inflammation responses.
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