2013 Fiscal Year Final Research Report
Alterations in Intercalated Disk Proteins Contribute to the Development of Lethal Arrhythmias
| 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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| 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 |
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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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Research Products
(23 results)
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[Presentation] Defective domain-domain interactions within ryanodine receptor as a critical cause of diastolic Ca2+ leak in failing hearts2011
Author(s)
立石裕樹,矢野雅文,末冨建,大野誠,徐暁娟,内海仁志,奥田真一,小田哲郎,小林茂樹,山本健,池田安宏,大草知子,松﨑益德,池本憲章
Organizer
第21回山口大学医学部第二内科飛翔会循環器研究会
Place of Presentation
宇部
Year and Date
2011-10-08
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[Presentation] New Diagnostic Test for Arrhythmogenic Right Ventricular Cardiomyopathy2011
Author(s)
Tadamitsu Nakashima, Tomoko Ohkusa, Masaaki Yoshida, Jutaro Yamada, Takayuki Okamura, Takeshi Ueyama, Toshiro Miura, Akihiko Shimizu, Minoru Horie, Masunori Matsuzaki
Organizer
The 28th Annual Scientific Meeting of the Japanese Society of Electrocardiology & The 26th Annual Meeting of the Japanese Heart Rhythm Society & The 4th Asia Pacific Heart Rhythm Society(APHRS)Scientific Session
Place of Presentation
Fukuoka(Jpn J Electrocardiol 31[Suppl 4] : 209)
Year and Date
2011-09-18
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