Modifiable Effects of Rapamycin on Vascular Remodeling via Repair of Oxidative DNA Damage
| 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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Report
(3 results)
Research Products
(56 results)
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[Journal Article] Edaravone diminishes free radicals from circulating neutrophils in patients with ischemic brain attack.2006
Author(s)
Aizawa H, Makita Y, Sumitomo K, Aburakawa Y, Katayama T, Nakatani- Enomoto S, Suzuki Y, Fujiwara K, Enomoto H, Kuroda K, Kimura T, Yahara 0, Koyama S, Maruyama J, Nakamura M, Hasebe N, Kikuchi K
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Journal Title
Intern Med 45(1)
Pages: 1-4
NAID
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Fujiwara K,Enomoto H,Kuroda K,Kimura T,Yahara O,Koyama S,Maruyama J,Nakamura M, Hasebe N,Kikuchi K Edaravone diminishes free radicals from circulating neutrophils in patients with ischemic brain attack.2006
Author(s)
Aizawa H, Makita Y, Sumitomo K, Aburakawa Y, Katayama T, Nakatani-Enomoto S, Suzuki Y
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Journal Title
Intern Med 45(1)
Pages: 1-4
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Positive delayed enhancement of cardiac MR Imaging and negative uptake of 18F-FDG PET Indicates damaged myocardial substrate of ventricular tachycardia in cardiac sarcoidosis circulation,2007
Author(s)
Sakamoto N, Kawamura Y, Matsuki M, Kanno T, Yamaki M, Tanabe Y, Natori S, Takei T, Sato N, Aburano T, Kikuchi K, Hasebe N
Organizer
American Heart Association 2007 Scientific Sessions
Place of Presentation
Orland, FL, USA
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] Positive delayed enhancement of cardiac MR Imaging and negative uptake of 18F-FDG PET Indicates damaged myocardial substrate of ventricular tachycardia in cardiac sarcoidosis circulation2007
Author(s)
Sakamoto N, Kawamura Y, Matsuki M, Kanno T, Yamaki M, Tanabe Y, Natori S, Takei T, Sato N, Aburano T, Kikuchi K, Hasebe N
Organizer
American Heart Association 2007 Scientific Sessions
Place of Presentation
Orland, FL, USA
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Thermal treatment attenuates vascular atherosclerosis and lowers blood pressure in spontaneously hypertensive rats2006
Author(s)
Tashiro, N, Okada M, Izawa K, Aizawa Y, Kawabe J, Sumitomo K, Fujino T, Fukuzawa J, Hasebe N, Kikuchi K
Organizer
The 21 st Scientific Meeting of the International Socelty of Hypenension
Place of Presentation
Fukuoka, Japan
Description
「研究成果報告書概要(和文)」より
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[Presentation] Macrophage Migration Inhibitory Factor and lschemia-Induced Angiogenesis2006
Author(s)
Fukuzawa J, Sakuragi H, Koyama S, Nishihara J, Yao N, Fujino T, Wakamlya N, Haneda T, Hasebe N, Kikuchi K
Organizer
The 21 st Scientific Meeting of the International Socelty of Hypenension
Place of Presentation
Fukuoka, Japan
Description
「研究成果報告書概要(和文)」より
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[Presentation] Decreased Susceptibility to Glomerular Hypertrophy and Albuminuria in Thromboxane A2 Receptor Deficient Mice2006
Author(s)
Fujino T, Abe K, Nakagawa N, Yuhki K, Kawabe J, fukuzawa J, Hasebe N, Kikuchi K, Narumiya S, Ushikubi F
Organizer
The 21 st Scientific Meeting of the International Soceltyof Hypenension
Place of Presentation
Fukuoka, Japan
Description
「研究成果報告書概要(和文)」より
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[Presentation] Induction of CL-Pl, a Novel Vascular Endothelial Cell-Specific Scavenger Receptor,by Ischemia/Reperfusion and its Association with Oxidized LDL2006
Author(s)
Koyama S, Fukuzawa J, Ohtani K, Itabe H, Yao N, Sakuragi H, Hasebe N, Kikuchi K, Wakamlya N
Organizer
The 21 st Scientific Meeting of the International Socelty of Hypenension
Place of Presentation
Fukuoka, Japan
Description
「研究成果報告書概要(和文)」より
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[Presentation] Delayed Enhancement of Cardiac Magnetic Resonance Imaging Indicates Abnomality of Repolarization in Hypertrophic Cardiomyopathy with Ventricular Tachycardia2006
Author(s)
Sakamoto N, Kawamura Y, Matsuki M, Yamauchi, A, Kanno T, Yamaki M, Tanabe Y, Shunsuke Natori, Furano, Sato N, Kikucbi K, Hasebe N
Organizer
American Heart Association 2006 Scientifc Sessions
Place of Presentation
Chicago, IL, USA
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] Decreased Susceptibility to Glomerular Hypertrophy and Albuminuria in Thromboxane A2 Receptor Deficient Mice2006
Author(s)
Fujino T, Abe K, Nakagawa N, Yuhki K, Kawabe J, fukuzawa J, Hasebe N, Kikuchi K, Narumiya S, Ushikubi F
Organizer
The 21 st Scientific Meeting of the International Socelty of Hypenension
Place of Presentation
Fukuoka, Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Induction of CL-P1, a Novel Vascular Endothelial Cell-Specific Scavenger Receptor, by Ischemia/Reperfusion and its Association with Oxidized LDL2006
Author(s)
Koyama S, Fukuzawa J, Ohtani K, Itabe H, Yao N, Sakuragi H, Hasebe N, Kikuchi K, Wakamlya N
Organizer
The 21 st Scientific Meeting of the International Socelty of Hypenension
Place of Presentation
Fukuoka, Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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