Soluble Fas, an inhibitor of apoptosis, gene therapy using adenovirus vector for chronic congestive heart failure

可溶性Fas，一种细胞凋亡抑制剂，使用腺病毒载体进行基因治疗慢性充血性心力衰竭

• 批准号: 13670698
• 负责人: NISHIGAKI Kazuhiko
• 金额: $ 2.24万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670698/
• 关键词: 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

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.

血清可溶性Fas（sFas）可阻断Fas配体与细胞膜上Fas受体的结合，是细胞凋亡的抑制因子。采用扩张型心肌病模型UM-X 7.1仓鼠，通过后肢肌肉注射SFas腺病毒载体，对心力衰竭进行基因治疗.在该模型中，sFas基因治疗组在基因治疗后4周血清sFas水平显著高于Lac Z基因对照组（500 mg/ml vs 0）.然而，sFas基因治疗组（71%和50%）和Lac Z对照组（72%和48%）5周和10周后的生存率相似。3.基因治疗后10周，左室舒张末期内径、射血分数和舒张末期压无显著差异。此外，心脏重量，纤维化的程度，%的TUNEL阳性心肌细胞，和心肌细胞的横向尺寸并没有显示出显着的差异在两个groups.In结论，sFas基因治疗并不抑制心力衰竭的进展，在UM-X 7.1仓鼠，尽管血清sFas的显着增加。提示Fas配体系统与UM-X 7.1仓鼠扩张型心肌病的发生发展无关。

项目成果

Watanabe, Motohiro: "Relationship between thallium-201 myocardial SPECT and findings of endomyocardial biopsy specimens in dilated cardiomyopathy"Annals of Nuclear Medicine. 15. 13-19 (2001)

Watanabe、Motohiro：“扩张型心肌病中铊 201 心肌 SPECT 与心内膜心肌活检标本结果之间的关系”核医学年鉴。

Motohiro Watanabe, Kohshi Gotoh, Kenshi Nagashima, Yoshihiro Uno, Toshiyuki Noda, Kazuhiko Nishigaki, Genzou Takemura, Motoo Kanoh, Norio Yasuda, Yasushi Ohno, Shinya Minatoguchi, Hisayoshi Fujiwara: "Relationship between thallium-201 myocardial SPECT and

Motohiro Watanabe、Kohshi Gotoh、Kenshi Nagashima、Yoshihiro Uno、Toshiyuki Noda、Kazuhiko Nishigaki、Genzou Takemura、Motoo Kanoh、Norio Yasuda、Yasushi Ohno、Shinya Minatoguchi、Hisayoshi Fujiwara：“铊 201 心肌 SPECT 与

Masanori Kawasaki, Hisato Takatsu, Toshiyuki Noda, Yoko Ito, Akihisa Kunishima, Masazumi Arai, Kazuhiko Nishigaki, Genzou Takemura, Norihiko Morita, Shinya Minatoguchi, Hisayoshi Fujiwara: "Noninvasive quantitative tissue characterization and two-dimensio

Masanori Kawasaki、Hisato Takatsu、Toshiyuki Noda、Yoko Ito、Akihisa Kunishima、Masazumi Arai、Kazuhiko Nishigaki、Genzou Takemura、Norihiko Morita、Shinya Minatoguchi、Hisayoshi Fujiwara：“非侵入性定量组织表征和二维

Kawasaki, Masanori: "Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesion using ultrasound integrated backscatter. Comparison between histology and integrated backscatter images"Journal of th

Kawasaki，Masanori：“使用超声集成反向散射对人体动脉粥样硬化病变进行无创定量组织表征和二维颜色编码图。组织学与集成反向散射图像之间的比较”杂志

Takemura, Genzou: "Characterization of ultrastructure and its relation with DNA fragmentation in Fas-induced apoptosis of cultured cardiac myocytes"Journal of Pathology. 193. 546-556 (2001)

Takemura, Genzou：“Fas 诱导的培养心肌细胞凋亡中超微结构的表征及其与 DNA 断裂的关系”病理学杂志。