| Project/Area Number |
15390247
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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 |
Circulatory organs internal medicine
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| Research Institution | Ehime University |
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Principal Investigator |
HORIUCHI Masatsugu Ehime University, School of Medicine, Professor, 医学部, 教授 (40150338)
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| Co-Investigator(Kenkyū-buntansha) |
IWAI Masaru Ehime University, School of Medicine, Associate professor, 医学部, 助教授 (00184854)
MOGI Masaki Ehime University, School of Medicine, Lecturer, 医学部, 講師 (20363236)
浜井 盟子 愛媛大学, 医学部, 助手 (20180929)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2003: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | Angiotensin / AT2 receptor / Vascular injury / Signal transduction / Oxidative stress / Cell proliferation / Transgenic mouse / AT1受容体 / 受容体 / シグナル / 動脈硬化 / 血管リモデリング / 炎症 / 血管平滑筋 |
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| Research Abstract |
The cardiovascular actions of angiotensin II (Ang II) are mainly mediated by the Ang II type 1 (AT_1) receptor. We cloned a novel AT_1 receptor-associated protein (ATRAP) using a yeast two-hybrid screening system. To explore the role of ATRAP in vascular remodeling, we developed transgenic mice for mouse ATRAP-cDNA, and examined remodeling after inflammatory vascular injury induced by polyethylene-cuff placement. In ATRAP transgenic (ATRAP-Tg) mice, ATRAP mRNA was increased 3- to 4-fold in the heart, aorta and femoral artery. ATRAP-Tg mice showed no significant change in body weight, systolic blood pressure, heart rate and heart-to-body weight ratio. However, cell proliferation and neointimal formation in the injured artery were attenuated in ATRAP-Tg mice. The increase in NADPH oxidase activity and the expression of p22^<phox>, an NADH/NADPH oxidase subunit, after cuff placement was also attenuated in ATRAP-Tg mice. Moreover, activation of extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription (STAT)1, and STAT3 after cuff placement were significantly reduced in ATRAP-Tg mice. In addition, we observed that cardiac hypertrophy induced by pressure-overload and Ang II infusion was attenuated in ATRAP-Tg mice, and that pressor response to Ang II was also decreased in ATRAP-Tg mice. These results suggest that ATRAP plays an important role in cardiovascular remodeling as a negative regulator.
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