Regulation of Notch signal pathway in vascular lesions
| Project/Area Number |
21590950
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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 | Nagoya University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
CHENG Xian Wu 名古屋大学, 医学系研究科, 准教授 (30378228)
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| Co-Investigator(Renkei-kenkyūsha) |
MUROHARA Toyoaki 名古屋大学, 医学系研究科, 教授 (90299503)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 分子血管病態学 / 動脈硬化 / Notchシグナル / 平滑筋 / 単球 |
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| Research Abstract |
Notch1 signaling plays pleiotropic roles in organogenesis in the developmental state. However, the pathophysiological role of Notch1 in vascular diseases has been unknown. Notch1 expression was evident in new vessels, inflammatory cells, and smooth muscle cells in arterial specimens from patients with arteriosclerosis obliterans and Buerger disease. We observed reduced neointimal formation followed by carotid artery injury in general and smooth muscle cell (SMC)-specific Notch1 heterozygous deficient mice. Notch1 signaling would be involved in proliferation, migration, and apoptosis of SMCs. We also testified the effects of Notch signal inhibitor, a gamma-secretase inhibitor (GSI: LY-411575) on suppression of atherosclerotic lesion in Apolipoprotein E deficient mice. Indeed GSI treatment suppressed infiltration of inflammatory cells and atherosclerotic lesion formation. Thus Notch1 signaling would be a potential target for vascular diseases.
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Report
(4 results)
Research Products
(44 results)
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[Journal Article] Impact of acarbose on carotid intima-media thickness in patients with newly diagnosed impaired glucose tolerance or mild type 2 diabetes mellitus: A one-year, prospective, randomized, open-label, parallel-group study in Japanese adults with established coronary artery disease.2010
Author(s)
Koyasu M, Ishii H, Watarai M, Takeshita K, Amano T, Yoshikawa D, Matsubara T, Murohara T.
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Journal Title
Clin Ther.
Volume: 32(9)
Pages: 1610-7
Related Report
Peer Reviewed
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[Journal Article] Impact of acarbose on carotid intima-media thickness in patients with newly diagnosed impaired glucose tolerance or mild type 2 diabetes mellitus : A one-year, prospective, randomized, open-label, parallel-group study in Japanese adults with established coronary artery disease2010
Author(s)
Koyasu M, Takeshita K, Amano T, Yoshikawa D, Matsubara T, Murohara T, et al
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Journal Title
Clin Ther
Volume: 32
Pages: 1610-7
Related Report
Peer Reviewed
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[Journal Article] Mechanism of diastolic stiffening of the failing myocardium and its prevention by angiotensin receptor and calcium channel blockers.2009
Author(s)
Cheng XW, Okumura K, Kuzuya M, Jin Z, Nagata K, Obata K, Inoue A, Hirashiki A, Takeshita K, Unno K, Harada K, Shi GP, Yokota M, Murohara T.
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Journal Title
J Cardiovasc Pharmacol.
Volume: 54(1)
Pages: 47-56
Related Report
Peer Reviewed
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[Journal Article] Smooth muscle Notch1 mediates neointimal formation after vascular injury.2009
Author(s)
Takeshita K, Li Y(equal contribution), Liu PY, Satoh M, Oyama N, Mukai Y, Chin MT, Krebs L, Kotlikoff MI, Radtke F, Gridley T, Liao JK.
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Journal Title
Circulation.
Volume: 119(20)
Pages: 2686-92
Related Report
Peer Reviewed
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