Physiological function of apolipoprotein J in neointimal hyperplasia after vascular injury and atherosclerosis : Mechanism and application to treatment
| Project/Area Number |
16590701
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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 | Kagoshima University |
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Principal Investigator |
MIYATA Masaaki Kagoshima University, University Hospital Faculty of Medicine and Dentistry, Research Associate, 医学部・歯学部附属病院, 助手 (00347113)
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| Co-Investigator(Kenkyū-buntansha) |
TEI Chuwa Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (10163891)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | atherosclerosis / vascular remodeling / apolipoprotein J / restenosis / knockout mouse / transgenic mouse |
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| Research Abstract |
Neointimal hyperplasia is a major cause of restenosis after coronary intervention. We reported that apolipoprotein J/clusterin (apoJ) was dramatically induced in media and neointima after vascular injury, and expression of clusterin stimulated proliferation and migration of cultured vascular smooth muscle cell (SMC).
First, we investigated the physiological function of apoJ in neointimal hyperplasia after vascular injury. We used 3 different types of mice as follows ; apoJ transgenic mice overexpressing apoJ in vessel-selective manner (apoJ-Tg), apoJ deficient mice (apoJ-KO), and wild C57BL6 mice. A non-restrictive cuff was placed around the femoral artery of each male mouse, and all mice were sacrificed 4 weeks later for the planimetric measurements of neointimal and medial area. The apoJ-Tg mice showed a significant increase of neointimal hyperplasia, and apoJ-KO mice showed a significant decrease of neointimal hyperplasia as compared with wild mice. In order to analyze the mechanism
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of promoting effect of apoJ on neointimal thickening after vascular injury, we performed immunohistochemical staining using antibodies against caspase-3, p53 and p27. The immunoreactivity for caspase-3 in neointima demonstrated no differences among 3 types of mice. However, apoJ-KO mice showed the increased immunoreactivities for both p53 and p27 in neointimal SMC as compared with apoJ-Tg and wild mice. These result suggest that apoJ deficiency may decrease neointimal hyperplasia by G1 arest of SMC.
Second, we investigated the physiological function of apoJ in atherosclerosis using apoJ-KO and apolipoprotein E-deficient mice (apoE-KO). ApoJ-KO was crossbred with apoE-KO, and double knockout mice (apoJ-KO/apoE-KO) was established. Mice were fed a chew diet and analyzed at 25 weeks of age. Atherosclerotic lesions in the aortic root were measured by a quantitative assay. The atherosclerotic lesion of apoJ-KO/apoE-KO mice were significantly smaller than that of apoE-KO. In order to analyze the mechanism of promoting effect of apoJ on atherosclerosis, we performed immunohistochemical staining using antibodies against NF-kB and B-MYB. The immunoreactivity for NF-kB and B-MYB in nuclei of smooth muscle cells in atherosclerotic lesions of apoJ-KO/apoE-KO was decresed compared to that of apoE-KO. ApoJ-deficiency decreased atherosclerosis via inhibition of NF-kB and B-MYB in apolipoprotein E-deficient mice, suggesting that apoJ is an atherogenic factor.
Inhibition of apoJ expression may provide a novel therapy to limit restenosis after coronary intervention or atherosclerosis. Less
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Report
(3 results)
Research Products
(14 results)
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[Journal Article] Expression of lectin-like oxidized LDL receptor-1 in smooth muscle cells after vascular injury.2006
Author(s)
Eto H, Miyata M, Kume N, Minami M, Itabe H, Orihara K, Hamasaki S, Biro S, Otsuji Y, Kita T, Tei C.
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Journal Title
Biochemical and Biophysical Research Communications. 341(2)
Pages: 591-598
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effects of repeated sauna treatment on ventricular arrhythmias in patients with chronic heart failure.2004
Author(s)
Kihara T, Biro S, Ikeda Y, Fukudome T, Shinsato T, Masuda A, Miyata M, Hamasaki S, Otsuji Y, Minagoe S, Akiba S, Tei C.
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Journal Title
Circ J. 68
Pages: 1146-1151
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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