| Project/Area Number |
20590886
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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 | Iwate Medical University |
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Principal Investigator |
SATOH Mamoru Iwate Medical University, 医学部, 准教授 (90305996)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 智範 岩手医科大学, 医学部, 講師 (30347851)
前沢 千早 岩手医科大学, 医学部, 准教授 (10326647)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 冠動脈疾患 / 血管内皮前駆細胞 / テロメア / 血管リモデリング / 酸化ストレス / スタチン / 動脈硬化 / microRNA / Toll様受容体 / RAS阻害薬 |
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| Research Abstract |
The present study has investigated microRNA biology concerning endothelial cellular injury and vascular inflammation, such as Toll-like receptor 4 (TLR4). Endothelial progenitor cells (EPCs) play an important role in the maintenance of vascular integrity. The physiological role of miR-221/222, a newly discovered class of small RNA, is closely linked to the proliferation of EPCs. In addition,this study demonstrates that lipid lowering therapy (LLT) with atorvastatin increases EPC numbers and decreases miR-221/222 levels in patients with CAD, possibly contributing to the beneficial effects of LLT with atorvastatin in this disorder.
TLR4 signal plays an important role in immunity in CAD. One of the let-7 family microRNAs, let-7i, directly regulates Toll-like receptor 4 (TLR4) expression and contributes to immune response. The miR-146a / b regulates TLR4 downstream molecules (IRAK1 and TRAF6). The present study has shown that miR-146a / b were expressed with TLR4 signal in CAD patients, and combined treatment with a statin and RAS blockade might affect these levels. In addition, let-7i played a negative regulator of TLR4 in patients with CAD, and atorvastatin affected TLR4 levels via let-7i.
This study demonstrates that treatment with ARB and atrovastatin decreases miR-146a / b and TLR4 signal in patients with CAD, possibly contributing to the anti-atherogenic effects of ARB and statins in this disorder.
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