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

血清可溶性Fas(SFas)可阻断Fas配体与细胞膜Fas受体的结合，是一种细胞凋亡抑制因子。对扩张型心肌病模型UM-X 7.1地鼠进行后肢肌肉注射sFas基因治疗心力衰竭。在该模型中，sFas基因治疗组在基因治疗4周后血清sFas水平显著高于Lac Z基因对照组(500 mg/mlvs0)。5周和10周后，sFas基因治疗组的存活率(71%和50%)与Lac Z对照组(72%和48%)相似。基因治疗10周后，LV舒张期内径、射血分数和舒张期内压无显著差异。此外，心脏重量、纤维化程度、TUNEL阳性心肌细胞的百分比和心肌细胞的横径在两组之间也没有显著差异。结论：sFas基因治疗不能抑制UM-X 7.1地鼠心力衰竭的进展，尽管血清sFas显著增加。提示Fas-Fas配体系统与UM-X 7.1地鼠扩张型心肌病的进展无关。

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.