| Project/Area Number |
11670729
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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 | Research Institute, National Cardiovascular Center |
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Principal Investigator |
KOMAMURA Kazuo Research Institute, NCVC, Dept of Cardiovascular Dynamics, Research Head, 循環動態機能部, 室長 (90311448)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Junichi Dept of Natrition and Physiological Chemistry, Osaka University Graduate School of Medicine, 医学部・分子病態栄養制御学, 教授 (10200156)
NAKAMUJRA Toshikazu Div. of Biochemistry, Dept of Oncology, Biomedical Research Center Osaka University Graduate School of Medicine, 医学部・腫瘍生化学, 教授 (00049397)
SUNAGAWA Kenji Research Institute, NCVC, Dept of Cardiovascular Dynamics, Director, 循環動態機能部, 部長 (50163043)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Dilated Cardiomyopathy / Heart Failure / Hepatocyte Growth Factor / Gene Transfection / Cardiac Remodeling / Myocardial Fibrosis |
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| Research Abstract |
1) We integrated rat Hepatocyte growth factor CDNA (rHGF) into PCAGGS plasmid vector, which has β-actin promoter and affinity to muscle cells (PCAGGS-rHGF). Likewise, we made PCAGGS-human HGR We could confirm expression of rHGF alone, and used this forthe experiment.
2) Ultrasound alone did not enhance transfection of rHGF. Sonoporation wrth microbubble made rat myocardial culture cells excrete HGF into medium.
3) We tried direct injection of genes into the heart of cardiomyopathic hamster. Reporter gene LacZ was found to be transfected in the myocaraium. There was no excretion of HGF protein into peripheral blood.
4) In vivo electroporation of LacZ and interleukin 5 into skeletal musde of hamster successfully transfected these genes. We employed this method, 6 pulses of 100V 50 ms, as a standard in vivo transfection method.
5) We tried in vivo electroponation of rHGF into tibialis anterior musde of cardiomyopathic hamsterTO-2 using the dose of 200, 400 and 800 μg. Dose of 800 μg. resulted into maximum blood concentration of HGF. This dose with standard in vivo transfection method turned out to be a sustained elevation of HGF concentration over 5 ng/mL. Cardiac function estimated by echo-Doppler improved in HGF-treated hamsters compared with normal control and placebo given hamsters. Myocardial fibrosis was suppressed and capillary density was increased in HGF-treated hamsters compared with placebo-given hamsters. Increase in MMP-1 activity might be attributable to one of possible mechanisms of beneficial effects of HGF treatment for heart failure in cardiomyopathic hamsters (submitted).
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