2008 Fiscal Year Final Research Report
Investigation for the new upstream treatment of arrhythmias targetinggap junction remodeling of cardiomyocyte
Project/Area Number |
19590818
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
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Research Institution | Yamaguchi University |
Principal Investigator |
OHKUSA Tomoko Yamaguchi University, 大学院・医学系研究科, 講師 (00294629)
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Project Period (FY) |
2007 – 2008
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Keywords | 不整脈 / ギャップ結合 / 治療 |
Research Abstract |
近年、ギャップ結合をはじめとする不整脈発生基盤の多くの因子が解明され、不整脈発生基質に焦点をあてたupstream 治療の重要性が注目されている。本研究はでin vivo(心肥大/心不全モデル動物)およびin vitro(培養心筋細胞)の実験系を用いて、心房筋・心室筋ギャップ結合の質的・量的変化、それを調節するRAA系とその下流因子の解析、同時に電気生理学的特性の変化を解析し、不整脈の発生・維持機構を分子生物学・生化学・生理学的に同時に解明する新しいアプローチを試みる研究を行った。従来、不整脈の発生・維持に関与するメカニズムの研究は、細胞膜上のチャネル特性を検討する電気生理学的アプローチが主であった。本研究結果は、不整脈の発生・維持に関与するメカニズムを、ギャップ結合リモデリングに焦点をあて、RAA 系を中心とした情報伝達系を解析し、ギャップ結合制御を目的とした不整脈の新しい治療薬の開発につながり、upstream治療に大きく貢献すると思わ
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[Journal Article] Altered expression of connexin43contributes to the arrhythomogenicsubstrate during the development of heartfailure in cardiomyopathic hamster2008
Author(s)
Sato T, Ohkusa T, Honjo H, Suzuki S,Yoshida M, Ishiguro YS, Nakagawa H,Yamazaki M, Yano M, Kodama I, Matsuzaki M
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Journal Title
Am JPhysiol Heart Circ Physiol 294
Pages: 174-1182
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[Journal Article] Alfdosterone modulates If current throughgene expression in cultured neonatal ratventriculat myocytes2007
Author(s)
Muto T, Ueda N, Opthof T, Ohkusa T,Nagata K, Suzuki S, Tsuji Y, Horiba M, LeeJK, Honjo H, Kamiya K, Kodama I, Yasui K.
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Journal Title
Am J Physiol Heart Circ Physiol 293
Pages: H2710-H2718
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[Presentation] Abnormally TightDomain-Domain Interaction at MutationSite could be a Primary Cause ofCatecholaminergic PolymorphicVentricular Tachycardia2009
Author(s)
Takeshi Suetomi, Masafumi Yano, MakotoOno, Xiaojuan Xu, Hitoshi Uchinoumi,Hiroki Tateishi, Shinichi Okuda, MasahiroDoi, Shigeki Kobayashi, Takeshi Yamamoto,Yasuhiro Ikeda, Tomoko Ohkusa, MasunoriMatsuzaki
Organizer
The 73rd AnnualScientific Meeting of The JapaneseCirculation Society
Place of Presentation
Osaka
Year and Date
2009-03-20
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[Presentation] Defective Inter-domain Interaction mayCause Spontaneous Ca^<2+> Release via ReducedAffinity of Calmodulin Binding to RyR2 inFailing Hearts Failing Hearts2009
Author(s)
Makoto Ono, Masafumi Yano, TakeshiSuetomi, Xiaojuan Xu, Hitoshi Uchinoumi,Shinichi Okuda, Masahiro Doi, ShigekiKobayashi, Takeshi Yamamoto, YasuhiroIkeda, Tomoko Ohkusa, Masunori Matsuzaki,
Organizer
The 73rd Annual ScientificMeeting of The Japanese CirculationSociety
Place of Presentation
Osaka
Year and Date
2009-03-20
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[Presentation] Defective Inter-domain Interaction MayCause Spontaneous Ca^<2+> Release Via ReducedAffinity of Calmodulin Binding to RyR2 inFailing Hearts2008
Author(s)
Makoto Ono, Masafumi Yano, TakeshiSuetomi, Xiaojuan Xu, Hitoshi Uchinoumi,Hiroki Tateishi, Shinichi Okuda, ShigekiKobayashi, Takeshi Yamamoto, YasuhiroIkeda, Tomoko Ohkusa, Masunori Matsuzaki
Organizer
Scientific Sessions 2008of American Heart Association
Place of Presentation
New Orleans
Year and Date
2008-11-08
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[Presentation] Abnormally Tight Domain-DomainInteraction at Mutation Site Could be aPrimary Cause of CatecholaminergicPolymorphic Ventricular Tachycardia : Insight from RyR2 S2246L/+Knock-In MouseModel2008
Author(s)
Takeshi Suetomi, Masafumi Yano,Xiaojuan Xu, Makoto Ono, Hitoshi Uchinoumi,Hiroki Tateishi, Shinichi Okuda, ShigekiKobayashi, Takeshi Yamamoto, YasuhiroIkeda, Tomoko Ohkusa, Masunori Matsuzaki
Organizer
Scientific Sessions 2008 ofAmerican Heart Association
Place of Presentation
New Orleans
Year and Date
2008-11-08
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[Presentation] Decreased Affinity of CalmodulinBinding to RyR2 May Cause Leaky Channel inCPVT-Associated Mutation : Insight fromRyR^<2R2474s/+> Knock-In Mouse Model2008
Author(s)
Xiaojuan Xu, Masafumi Yano, TakeshiSuetomi, Makoto Ono, Hitoshi Uchinoumi,Hiroki Tateishi, Shinichi Okuda, ShigekiKobayashi, Takeshi Yamamoto, YasuhiroIkeda, Tomoko Ohkusa, Masunori Matsuzaki
Organizer
Scientific Sessions 2008 of American Heart Association
Place of Presentation
New Orleans
Year and Date
2008-11-08
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[Presentation] Mutation-Linked, DefectiveInter-Domain Interaction within theCardiac Ryanodine Receptor as a CriticalCause of Catecholaminergic PolymorphicVentricular Tachycardia (CPVT)2008
Author(s)
Hitoshi Uchinoumi, Masafumi Yano,Takeshi Suetomi, Xiaojuan Xu, Makoto Ono,Hiroki Tateishi, Shinichi Okuda, ShigekiKobayashi, Takeshi Yamamoto, YasuhiroIkeda, Tomoko Ohkusa, Masunori Matsuzaki
Organizer
Scientific Sessions 2008 of American HeartAssociation
Place of Presentation
New Orleans
Year and Date
2008-11-08
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[Presentation] 慢性心不全患者における酸化ストレスマーカー : 尿8-hydroxy-2-deoxyguanosine(8-OHdG)の有用性について2008
Author(s)
小林茂樹,須佐建央,河村修二,田中健雄,伊藤真一,吉賀康裕,岡村誉之,大草知子,矢野雅文,藤井崇史,松崎益徳
Organizer
第105 回日本内科学会総会・講演会
Place of Presentation
東京
Year and Date
2008-04-11
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[Presentation] Urinary8-Hydroxy-2' -Deoxyguanosine LevelReflects Symptomatic Status and Severityof Systolic Dysfunction in Patients withChronic Heart Failure2008
Author(s)
Takehisa Susa, Shigeki Kobayashi, ShujiKawamura, Takeo Tanaka, Shinichi Itoh,Yasuhiro Yoshiga, Takayuki Okamura,Tomoko Ohkusa, Masafumi Yano, TakashiFujii, Masunori Matsuzaki
Organizer
The 72nd AnnualScientific Meeting of the JapaneseCirculation Society
Place of Presentation
Fukuoka
Year and Date
2008-03-28
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[Presentation] Urinary 8-Hydroxy-2'-DeoxyguanosineLevel Reflects Symptomatic Status andSeverity of Systolic Dysfunction inPatients with Chronic Heart Failure2007
Author(s)
Takehisa Susa, Shigeki Kobayashi, SyujiKawamura, Shinichi Itoh, Takeo Tanaka,Yasuhiro Yoshiga, Tsuyoshi Ueyama,Takayuki Okamura, Tomoko Ohkusa, MasafumiYano, Takashi Fujii, Masunori Matsuzaki
Organizer
Scientific Sessions 2007 of American HeartAssociation
Place of Presentation
Orland
Year and Date
2007-11-05
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[Presentation] DefectiveDomain-Domain Interaction BetweenC-terminal and Central Regions ofRyanodine Receptor as a Critical Cause ofDiastolic Ca^<2+> Spark in CanineCardiomyocytes2007
Author(s)
Hiroki Tateishi, 、Masafumi Yano, MakotoOhno, Xiaojuan Xu, Hitoshi Uchinoumi,Mamoru Mochizuki, Shigeki Kobayashi,Takeshi Yamamoto, Yasuhiro Ikeda, TomokoOhkusa, Masunori Matsuzaki
Organizer
The 11th Annual ScientificMeeting of the Japanese Heart FailureSociety
Place of Presentation
Chiba
Year and Date
2007-09-09
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[Presentation] SpontaneousCa^2+ Sparks Through Mutated RyanodineReceptor as a Critical Cause ofCatecholaminergic PolymorphicVentricular Tachycardia2007
Author(s)
Hitoshi Uchinoumi, Masafumi Yano,Makoto Ohno, Xiaojuan Xu, Hiroki Tateishi,Mamoru Mochizuki, Shigeki Kobayashi,Takeshi Yamamoto, Yasuhiro Ikeda, TomokoOhkusa, Masunori Matsuzaki
Organizer
The 11th AnnualScientific Meeting of the Japanese HeartFailure Society
Place of Presentation
Chiba
Year and Date
2007-09-09
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[Presentation] Young Investigator's Award forInternational Students Finalists Lecture「Decreased affinity of calmodulinbinding to RyR2 may cause leaky channel inCPVT-associated mutation : Insight fromRyR2^<R2474S/+> Knock-in mouse model」2007
Author(s)
Xiaojuan Xu, Masafumi Yano, TakeshiSuetomi, Makoto Ono, Hitoshi Uchinoumi,Hiroki Tateishi, Shinichi Okuda, ShigekiKobayashi, Takeshi Yamamoto, YasuhiroIkeda, Tomoko Ohkusa, Masunori Matsuzaki
Organizer
The 73rd Annual Scientific Meeting of The Japanese Circulation Society
Place of Presentation
Osaka
Year and Date
2007-03-20