| Project/Area Number |
13670748
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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 | Yokohama City University (2002)
Tokyo Women's Medical University (2001) |
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Principal Investigator |
MINAMISAWA Susumu Yokohama City University, Physiology, Associate Professor, 医学部, 助教授 (40257332)
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| Co-Investigator(Kenkyū-buntansha) |
KASANUKI Hiroshi Tokyo Women's Medical University, Cardiology, Professor, 循環器科, 教授 (40096574)
MATSUOKA Rumiko Tokyo Women's Medical University, Pediatric Cardiology, Assistant Professor, 循環器小児科, 講師 (50120051)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Heart Failure / calcium cycling / arrhythmias / sarcoplasmic reticulum / electrophysiology / phospholamban |
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| Research Abstract |
Calcium is not only indispensable for normal muscle contraction and relaxation but also an important second messenger of various signaling pathways in the heart. A growing body of evidence has shown that Ca^<2+> homeostasis and Ca^<2+> -dependent signaling pathways play a pivotal role in the development of cardiac hyperirophy and heart failure. The enhancement of Ca^<2+> uptake via cardiac SR Ca^<2+> ATPase (SERCA2a) may have potential therapeutic value for heart failure. Arrhythmogenesis is a potential adverse effect of the enhancement of Ca^<2+> uptake. To establish the safety of this treatment, we examined the susceptibility of arrhythmias in phospholamban knockout mice which display the almost maximal SERCA2a activity. The programmed electrophysiological study and telemetry electrocardiography revealed that phospholamban ablation was not susceptible to arrhythmias in mice. The data indicated that phospholamban ablation could be a novel therapeutic strategy for heart failure without the potent risk of arrhythmogenesis.
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