| Project/Area Number |
12670678
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
SUGANO Masahiro Medical Institute of Bioregulation Kyushu Univ. Research Associate, 生体防御医学研究所, 助教授 (20206395)
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| Co-Investigator(Kenkyū-buntansha) |
HATAKENAKA Masamitu Medical Institute of Bioregulation Kyushu Univ. Assistant Professor, 生体防御医学研究所, 講師 (40253413)
MAKINO Naoki Medical Institute of Bioregulation Kyushu Univ. Professor, 生体防御医学研究所, 教授 (60157170)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Tumor necrosis factor / Soluble TNF receptor 1 / Apoptosis / Angiogenesis / Endothelial cells / Myocardial infarction / TNF-alphaレセプタ-1 / 酸化LDL |
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| Research Abstract |
1) Growth of HUVEC transfected with sTNFRI vector also increased significantly compared to those transfected with control vector. Accumulation of sTNFRI significantly increased in conditioned medium from HUVEC transfected with sTNFRI vector compared to those transfected with control vector. HUVEC transfected with sTNFRI vector not only increased sTNFRI but also prevented shedding of sTNFRI from TNFRI. The TNF-a-induced internucleosomic fragmentation was also significantly prevented in HUVEC transfected with sTNFRI vector compared to those transfected with control vector.
2) The incubation of HUVEC with oxLDL increased LOX-1 mRNA levels and CPP32-like protease activity, and induced apoptosis. Preincubation of HUVEC with nifedipine before incubation with oxLDL significantly suppressed the increase in LOX-1 mRNA levels and CPP32-like protease activity, preventing (7)___ in a dose-dependent manner. These results suggest that nifedipine blocks the suicide pathway leading to the apoptosis of endothelial cells by decreasing LOX-1 mRNA levels and CPP32-like protease activity.
3) Here we report that direct injection of a sTNFRI expression plasmid DNA to the myocardium reduces infarct size in experimental rat AMI. Treatment with sTNFRI expression plasmid DNA reduced the TNF-alpha bioactivity in the myocardium and the apoptosis of cardiomyocytes. These findings suggest that the anti-TNF-alpha therapy by sTNFRI can be a new strategy for treatment of AMI.
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