| Project/Area Number |
18590774
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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 | Kinki University (2007)
Kyoto University (2006) |
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Principal Investigator |
IWANAGA Yoshitaka Kinki University, School of Medicine, Lecturer (80360816)
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| Co-Investigator(Kenkyū-buntansha) |
SHIOI Tetsuo Kyoto University, Graduate School of Medicine, Lecturer (50360095)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Heart Failure / Adipose |
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| Research Abstract |
The endogenous peptide, apelin, has positive inotropic and vasodilatory and diuretic effects through APJ receptor. First, we have reported that cardiac apelin-APJ system was down-regulated in rats with heart failure and might be counter-regulated by cardiac angiotensin II system. Also, in humans, plasma apelin concentrations are reported to decrease in heart failure.
Therefore, we next tested the hypothesis that chronic apelin administration would prevent the progression of left ventricular (LV) remodeling and improve the survival in rat heart failure model.
Dahl salt-sensitive hypertensive rats were given high salt diet from 6 weeks of age. They were chronically treated with apelin (15 μ g/day) (APL group: n=9) or saline (CONT group: n=11) from the LV hypertrophic stage (11 weeks of age) until 21 weeks. There was no difference in blood pressure between the two groups through the course. The survival rate in APL group was improved at 21 weeks of age from 18.2% to 77.8% (log rank test: p<0.05). By echocardiography, LV end-diastolic dimension was smalle r(7.0mm vs. 8.0mm; p<0.05) and fractional shortening was preserved (46.2% vs. 31.5%; p<0.05) in APL group. In postmortem examination, LV hypertrophy was mildly suppressed and mRNA levels of BNP and endothelin-1 in LV was significantly decreased in APL group. Although APJ is a G protein-coupled receptor having high similarity with angiotensin II type 1 receptor, exogenous apelin administration did not evoke hypertrophic responses nor did it suppress hypertrophy induced by endothelin-1 in neonatal cardiac myocytes.
These results indicated chronic apelin administration has beneficial effects by preventing the progression of LV remodeling and dysfunction independent of suppressing LV hypertrophy in rats with heart failure and might have therapeutic potential in human heart failure.
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