| Project/Area Number |
09670750
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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 | THE KITASTO INSTITUTE (1998-2000)
Keio University (1997) |
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Principal Investigator |
AKAISHI Makoto THE KITASATO INSTITUTE DIRECTOR OF MEDICINE, 研究員 (90150961)
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| Co-Investigator(Kenkyū-buntansha) |
BABA Akiyasu THE KITASATO INSTITUTE, 研究員 (60296572)
SHIBATA Katsushi KEIO UNIVERSITY, 助手 (70296565)
島田 恵 社団法人 北里研究所, 北里研究所病院, 内科研究員 (50235628)
岡部 輝雄 慶應義塾大学, 医学部, 助手 (60255445)
小山田 和弘 慶應義塾大学, 医学部, 助手 (00245474)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | HVJ-liposome method / electrical activities / heart failure / luciferase / ion channel / myocardial infarction / Kv1.2 / Kv1.5 / 遺伝子導入 / 心房性利尿ホルモン受容体 / ダウンレギュレーション / 膜電位依存性Kチャネル / ラット心筋梗塞モデル / 膜電位依存性カリウムチャネル / Green Fluorescent Protein / 膜電位依存症カリウムチャネル / 不整脈モデル |
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| Research Abstract |
The aims of this study are (1) to establish the technique of in-vivo gene transfer using HVJ liposome, (2) to clarify the molecular mechanism for the pathogenesis of lethal ventricular arrhythmia by examining the electrophysiological and biochemical change in various mouse model of cardiac disease such as myocardial infarction and cardiac failure. (3) further, to restore the patho-electrophysiological phenotype by introducing the exogenous genes. Result 1 : High luciferase activity was observed in the cardiac myocyte which is introduced with luciferase reporter gene using HVJ liposome in vivo, indicating in-vivo gene transfer was successfully performed. Result 2 : The ventricular tachycardia/fibrillation was induced in mouse model of myocardial infarction (MI) by electrophysiological stimulation. Result 3 : All three types of natriuretic peptide receptor mRNAs (type A, Band C) were modulated in the progression of cardiac remodeling induced by MI.Especially, the A and B-natriuretic peptide receptor subtype mRNAs were down regulated in post MI-remodeled myocardium, indicating that there is the subtype specific transcriptional regulatory mechanism in the heart. Result 4 : Kv1.2 and Kv1.5 gene are differently regulated between atrial and ventricular tissues in the progression of cardiac remodeling induced by MI.This transcription change in voltage-gated K+ channel might be implicated in the patho-electrophysiological change observed in post MI-remodeled heart. Summary : We have successfully introduced exogenous gene in-vivo by using HVJ liposome. The ventricular tachycardia/fibrillation was observed in mouse model of myocardial infarction. Transcriptional change of voltage-gated K+ channel or natriuretic peptide receptor genes is thought to be closely related to the pathogenesis of post-MI remodeled heart. Furthermore, we are planning to restore the patho-electrophysiological change by introducing the exogenous genes to the diseased heart muscle.
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