Soluble Fas, an inhibitor of apoptosis, gene therapy using adenovirus vector for chronic congestive heart failure
| Project/Area Number |
13670698
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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 | Gifu University |
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Principal Investigator |
NISHIGAKI Kazuhiko University Hospital, Lecturer, 医学部附属病院, 講師 (60198447)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Hisayoshi School of Medicine, Professor, 大学院・医学研究科, 教授 (80115930)
KOSAI Kenichiro School of Medicine, Associate Professor, 医学部, 助教授 (90258418)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | sFas gene therapy / heart failure / UM-X 7.1 hamster / apoptosis / necrosis / serum sFas / ventricular dilatation / fibrosis / 遺伝子治療 / 血漿可溶性Fas |
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| Research Abstract |
Serum soluble Fas (sFas) can block the binding between Fas-ligand and Fas-receptor on cell membrane, and is an inhibitor of apoptosis. SFas gene therapy using adenovirus vector injected into the hindlimb muscles was performed for cardiac failure of UM-X 7.1 hamster, a model of dilated cardiomyopathy.
1. In this model, serum sfas level 4 weeks after gene therapy was markedly increased in the sFas gene therapy group, compared to the control group with Lac Z gene (500mg/ml vs 0 of control).
2. However, survival rate 5 and 10 weeks later was similar between the sFas gene therapy group (71% and 50%) and the Lac Z control group (72% and 48%).
3. There was no significant difference of LV endodiastolic dimension, ejection fraction, and endodiastolic pressure 10 weeks after gene therapy. Also, heart weight, the extent of fibrosis, the % of TUNEL-positive cardiomyocytes, and the transverse size of cardiomyocytes did not show significant differences between the two groups.
In conclusion, sFas gene therapy does not inhibit the progression of cardiac failure in UM-X 7.1 hamster, in spite of marked increase of serum sFas. This suggests that Fas-Fas ligand system is independent of the progression of dilated cardiomyopathy of UM-X 7.1 hamster.
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Report
(3 results)
Research Products
(12 results)
