| Project/Area Number |
23591081
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kyushu University (2013)
Yamaguchi University (2011-2012) |
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Principal Investigator |
OHKUSA Tomoko 九州大学, 大学病院, 研究員 (00294629)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 不整脈 / 介在板 / ギャップ結合 / 心不全 / レニン・アンジオテンシン系 / intercalated disk / gap junction / adhesion junction / arrhythmia / レニン・アンジオテンシン・アルドステロン系 |
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| Research Abstract |
The intercalated disc (ID) contains adhesion junctions (AJs) and connexin (Cx) gap junctions (GJs). We investigated ID remodeling during development of heart failure in UM-X7.1 cardiomyopathic hamsters (UMX). We investigated the effect of angiotensin II blockade (ARB) on ID remodeling. At 10w, ~20% of UMX died suddenly, and VT/VF was inducible in ~30%. At 10w, the dispersion of action potential duration (APD) was increased. At 20w showed significant reduction of cardiac space constant, a decrease in conduction velocity, and an increase in APD dispersion. The expression of Cx43 was reduced and Ser255-phosphorylated Cx43 was increased at 20w. Qualitative and quantitative Cx43 alterations create serious arrhythmogenic substrate. The changes in beta-catenin preceded Cx43 alterations. At 10w, the nuclear expression of beta-catenin was remarkably decreased. ARB improved these alterations in ID proteins and physiological properties. ARB was an effective treatment of ID remodeling.
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