| Project/Area Number |
09670755
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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 | TEIKYO UNIVERSITY |
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Principal Investigator |
TAKESHITA Satoshi TEIKYO UNIVERSITY SCHOOL OF MEDlCINE DEPARTMENT OF MEDICINE Instructor, 医学部, 講師 (90271288)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | gene therapy / myocardial ischemia / angiogenesis / angrogenesis / 遺伝子治療 / 心筋梗塞 / ラット |
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| Research Abstract |
Background Recent investigations have demonstrated the ability of vascular endothelial growth factor (VEGF) to augment the development of collateral arteries in vivo. in vitro studies have suggested that the use of VEGF also improves the endothelium-dependent relaxation of collaterals at the microvascular level. The purpose of this study was to determine in vivo the extent to which vasomotor responses of collateral microvessels are altered following VGEF-treatment
Methods and Results Ischemia was indiced in the hinclimb of 35 rats by excision of the femoral artery. Immediately thereafter, 400 mug of a plasmid encoding VEGF or beta-galactosidase (control) was transfected into limb muscles. Four weeks later, synchrotron radation microangiography, with a spatial resolution of 30 mum, was performed to document the reactivity of collateral microvessels. Administration of the endothelium-dependent vasodilator acetylcholine failed to induce dilation of collateral microvessels in control animals. By contrast, profound dlation of collaterals was observed after acetylcholine in VEGF-treated animals. This response was evident in vessels with a linear appearance but not in those with an undulating appearance. The resulting blood flow in the ischemic limb after administration of acetylcholine in the control animals was only 64.6*17.0% of that of the contralateral normal limb, whereas blood flow was augmented to 106.11*8.4% in VEGF-treated animals (P<.05).
Conclusions These results demonstrate in vivo that the use of VEL3F restores impaired vasomotor responses in some types of collateral microvessels, which may help to provide a basis for understanding the microcirculation following therapeutic angiogenesis with VEGE.
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