| Project/Area Number |
04670522
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ITO Hiroshi The 2nd Department of Medicine Tokyo Medical and Dental University Assistant Professor, 医学部, 助手 (10232464)
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| Co-Investigator(Kenkyū-buntansha) |
HIROE Michiaki The 2nd Department of Medicine Tokyo Medical and Dental University Lecturer, 医学部, 講師 (80101872)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Insulin-like growth factors / cardiomyocytes / mRNA / muscle specific genes / endothelin-1 / angiotensin II / 心筋症 / 心筋生検 / RT-PCR / Insulin-like growth factor-I / cultured cardiocytes / skeletal α-actin / gene expression / endothelih-1 / hypertrophy / endomyocardial biopsy / PCR / 心筋肥大 / ラット培養心筋細胞 / オートクリン機構 / アンギオテンシンII / ETA レセプターアンタゴニスト |
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| Research Abstract |
(1) Hypertrophy of cardiomyocytes by insulin-like growth factors
We examined whether Insulin-like growth factors(IGFs) induce hypertrophy in cultured neonatal rat cardiomyocytes. Both IGF-I and II increased mRNA levels for several muscle specific genes (skeletal alpha-actin, myosin light chain 2, and troponin I). The cell size and protein synthesis was dose-dependently increase by IGFs. Binding study using ^<125>I-IGF-I revealed the presence of specific binding sites for IGFs in rat cardiomyocytes. These results suggest that IGF-I directly causes cardiac hypertrophy.
(2) Endothelin-1 as cardiac hypertrophy promoting factor.
We investigated the possible autocrine/paracrine role of endogenous endothelin-1(ET-1) in angiotensin II(ANG II)-induced hypertorophy of neonatal rat cardiomyocytes. ppET-1 mRNA was abundantly expressed and upregulated by ANG II in cardiomyocytes. Both ET-1 and ANG II stimulated increase [^3H]leucine incorporation into cardiomyocytes, whose effects were similarly inhibited by ETA receptor antagonist(BQ123). Introduction of antisense sequence against coding region of ppET-1 mRNA into cardiomyocytes resulted in complete blockade with ppET-1 mRNA levels and [^3H]leucine incorporation stimulated by ANG II.These results suggest that endogenous ET-1 locally generated by cardiomyocytes may contribute to ANG II-induced cardiac hypertrophy via an autocrine/paracrine fashion.
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