| Project/Area Number |
22390265
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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 |
Thoracic surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
MINAKATA Kenji 京都大学, 大学院・医学研究科, 講師 (60539675)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Tadashi 京都大学, 大学院・医学研究科, 准教授 (40281092)
MARUI Akira 京都大学, 大学院・医学研究科, 准教授 (60402856)
TABATA Yasuhiko 京都大学, 再生医科学研究所, 教授 (50211371)
YAMAHARA Kenichi 国立循環器病研究センター, 再生医療部, 室長 (50450888)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2010: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| Keywords | ミクロRNA / 血管平滑筋 / 内膜肥厚 / miRNA / 虚血性心疾患 / 冠動脈バイパス術 / エレクトロポレーション / 血管リモデリング / レンチウイルス |
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| Research Abstract |
Intimal hyperplasia is the major cause of veingraft disease. Proliferation and migration of smooth muscle cells (SMCs) into the intima are key mechanism in this process. Recent studies have revealed that microRNA-145(miR-145) is a specific mediator in the regulation on phenotype of SMCs, proliferative or differentiative. We aimed to investigate the impact of miR-145 on intimal hyperplasia with rabbit vein graft disease model using electroporation-mediated gene transfer. We harvested right jugular vein of male Japanese white rabbit and injured the endothelium by balloon catheter. Vein graft was transduced with miR-145 encoding plasmidsby electroporator and interposed at ipsilateral carotid artery. Fourweeks after surgery, we explanted the venous graft and performed histological studies (hematoxylin and eosin staining, and elastica van Gieson staining for elastic fiber). Intimal thickness and intima/media area ratio were evaluated. Furthermore, immunohistochemistry for mature smooth muscle marker myosin heavy chain smooth muscle-1 and -2 (SM-1 and SM-2) and proliferation marker Ki-67 were performed to study the degree of differentiation and proliferation of SMCs.MiR-145 transduction significantly reduced neointimal thickness and intima/media area ratio compared to the grafts without gene transfer. Immunohistochemistry revealed that miR-145 transduced grafts contained more SM-2 positive mature SMCs and less Ki-67 positive proliferating cells. Considering these results, we conclude that electroporation-mediated non-virus transfer of miR-145 into the vein bypass graft potently regulates SMC phenotype and would be promising to prevent intimal hyperplasia in vein graft disease.
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