| Project/Area Number |
21390252
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | National Cardiovascular Center Research Institute |
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Principal Investigator |
KISHIMOTO Ichiro 独立行政法人国立循環器病研究センター, 糖尿病・代謝内科, 医長 (80312221)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUDOME Takeshi 独立行政法人国立循環器病研究センター, 生化学部, 室長 (00443474)
KANGAWA Kenji 独立行政法人国立循環器病研究センター, 研究所, 所長 (00112417)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2011: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2009: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | グレリン / 心臓保護 / 自律神経 / 心筋梗塞 / 心不全 / 交感神経 / 糖尿病 / 肥満 / 生理活性ペプチド / 迷走神経 |
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| Research Abstract |
Ghrelin is an endogenous ligand for the growth-hormone secretagogues receptor(GHS-R). In addition to its role in the regulation of growth hormone(GH) release, the 28-amino acid peptide also stimulates food intake and induces adiposity. Since GHS-R is detected in the heart and blood vessels, the role of this peptide in the regulation of cardiovascular function has been suggested. Recently, we investigated the effect of daily peripheral ghrelin administration for 2 weeks in a rat model of myocardial infarction and found that ghrelin significantly attenuated cardiac dysfunction and remodeling induced by infarction. Interestingly, chronic administration of ghrelin dramatically suppressed the increase in heart rate and plasma noradrenaline concentration after infarction to the levels similar to sham-operated controls. The effects of ghrelin were accompanied by a decrease in the ratio of the low-to-high frequency spectra of heart rate variability. Moreover, we have also shown that one-shot subcutaneous administration of ghrelin in the very acute phase following infarction effectively rescues cardiac dysfunction/remodeling, prevents arrhythmias and significantly improves mortality. By the direct recoding of cardiac sympathetic nerve activity, it is demonstrated that early ghrelin administration suppresses cardiac sympathetic nerve activity excessively activated after infarction. Surprisingly, one-shot ghrelin administration in the acute phase of myocardial infarction improved cardiac dysfunction and sympathetic hyperactivity in the chronic phase. It is, therefore, suggested that ghrelin is potentially useful as a novel therapy for heart failure, arrhythmia and death in myocardial infarction, with its unique mechanism of action.
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