| Project/Area Number |
18590799
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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 | Asahikawa Medical College |
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Principal Investigator |
HASEBE Naoyuki Asahikawa Medical College, Faculty of Medicine, Professor (30192272)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Rapamicin / Drug Eluting Stent / Vascular Remodeling / Basic Excision Repair / AP endonuclease / Vascular Injury Model / Oxidative Stress / Vascular Inflamation |
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| Research Abstract |
For the assessment of modifiable effects of Rapamycin (sirolimus) on vascular remodeling via repair of oxidative DNA damage, we studied the effects of drug-eluting stent (DES) applied rapamicin on the suppression of neointimal formation in percutaneous coronary intervention. Implantation of DES enhanced production of reactive oxygen species (ROS) in neutrophils and suppressed inflammatory process. These protective actions of DES were enhanced by an angiotensin receptor blockade. We extracted RNA from isolated human leukocytes and purified DNA of AP endonuclease (Ape1/ref1), which is a major base excision repair (BER) enzyme for oxidative-damaged DNA. Using a specific plasmid and adenovirus, pcDNA/Ape1 and pcDNA/LacZ were transfected to injured vessels. At the site of wire-injured vessels, the expression of Ape1 gene was significantly enhanced compared to non-injured normal vessels, suggesting an important role of Ape1 in the process of vascular remodeling. These results suggested that antioxidative repair mechanism through the regulation of BER system may provide a novel antiatherosclerotic action. Regulation of vascular remodeling through the modification of oxidative DNA-BER system is a promising novel target of antiatherosclerotic therapy.
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