| Project/Area Number |
12670711
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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 | Fukuoka University |
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Principal Investigator |
KAI Hisashi Faculty of Phar. Sciences, Fukuoka University Research Associate, 薬学部, 助手 (50289550)
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| Co-Investigator(Kenkyū-buntansha) |
KAI Hisashi Kurume Univ., Cardiovascular Res. Institute, Associate Professor, 循環器病研究所, 助教授 (60281531)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | TGF-β / myocardial fibrosis / hypertension / diastolic dysfunction / pressure-overloaded hearts / HVJリポゾーム / HVJリポソーム / 可溶性TβRIIIgGキメラ遺伝子 / HVJリボソーム |
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| Research Abstract |
Excessive myocardial fibrosis impairs cardiac function in hypertensive hearts. Roles of transforming growth factor (TGF)-B in myocardial remodeling and cardiac dysfunction were examined (in press)ure-overloaded rats.
Pressure overload was induced by a suprarenal aortic constriction in Wistar rats. Fibroblast activation (proliferation and phenotype transition to myofibroblasts) was observed after day 3 and peaked at days 3-7. Thereafter, myocyte hypertrophy and myocWdial fibrosis developed by day 28. At day 28, echocardiography showed normal LV fractional shortening but the decreased early to late filling ratio of the transmitral Doppler velocity, and hemodynamic measurement revealed LV end-diastolic pressure elevation, indicating normal systolic but abnormal diastolic function. Myocardial TGF-B mRNA expression was induced after day 3, peaked at day 7, and remained modestly increased at day 28.An anti-TGF-B neutralizing antibody (NAb), which was intraperitoneally administered daily from 1 day before operation, inhibited fibroblast activation and subsequently prevented collagen mRNA induction and myocardial fibrosis, but not myocyte hypertrophy. NAb reversed diastolic dysfunction without affecting blood pressure and systolic function.
TGF-B plays a causal role in myocardial fibrosis and diastolic dysfunction through fibroblast activation in
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