| Project/Area Number |
06670747
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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 | Nippon Medical School |
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Principal Investigator |
TOMITA Yoshifumi Nippon Medical School, 1st Internal Medicine, Assistant, 医学部, 助手 (00180175)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAE Yasuhiro Nippon Medical School, 1st Internal Medicine, Assistant, 医学部, 助手 (10189102)
SEINO Yoshihiko Nippon Medical School, 1st Internal Medicine, Lecturer, 医学部, 講師 (10163073)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
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| Keywords | growth factor / FGF / TGFbeta / apoptosis / cardiomyopathy / model animal / cardiac hypertrophy / cardiomyopathy / cardiomyocyte / in situ hybridization / FGF(fibroblast growth factor) |
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| Research Abstract |
To clarify pathophysiological roles of FGF in idiopathic cardiomyopathy, LV endomyocardial biopsy specimens from 24 patients (9 HCM,12 DCM,and 3 hypertensive hypertrophy) and 6 controls were stained for acidic FGF (aFGF) and basic FGF using immunohistochemistry. Positive staining of acidic FGF was observed in myocytes of biopsy specimen from 15 of 21 (71%) cardiomyopathy patients, all hypertensive hypertrophy patients, but none of the controls (p<0.01 ; cardiomyopathy vs controls). Average diameter of myocytes was larger in patients with positive aFGF staining than those with negative staining. Percent area of fibrosis and capillary vessel density were not significantly different between two groups, however. intense expression of aFGF mRNA was observed in myocytes from the patients with positive aFGF protein.
The findings above mentioned were further ascertained by experimental study in cardiomyopathic animals. Syrian hamster BIO14.6 (aged 6 and 20 weeks) and control hamster (F1beta) with the matched age were used (n=12). Histological examination, western blot for aFGF protein, and immunohistochemistry using polyclonal anti-human acidic FGF and oplyclonal anti-human VEGF165 were evaluated. Immunostaining revealed marked accumulation of aFGF in myocytes from BIO 14.6 hamster, especially in degenerated myocytes. Positive staining of aFGF in myocytes were observed in 6/6 of BIO 14.6 hamsters, while in 1/6 of control hamster. Western blot for aFGF protein showed 19kD band was more apparent in myocardial extract of BIO 14.6 hamster than control hamster F1beta.
[Conclusion]
Expression of aFGF was significantly increased in the left ventricle of human idiopathic cardiomyopathy and hamster cardiomyopathy. It is suggested that aFGF might play an important role in myocyte hypertrophy and repair response of myocardial degeneration in animal cardiomyopathy. Further study is needed to clarify whether aFGF is ameliorating or deteriorating factor in cardiomyopathy.
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