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

血清可溶性Fas （sFas）可以阻断Fas配体与细胞膜上Fas受体的结合，是一种细胞凋亡抑制剂。采用腺病毒载体注射后肢肌肉对扩张型心肌病模型um - x7.1仓鼠心衰进行SFas基因治疗。在该模型中，基因治疗后4周，sfas基因治疗组血清sfas水平明显高于Lac Z基因对照组（500mg/ml vs 0对照）。然而，5周和10周后，sFas基因治疗组（71%和50%）与Lac Z对照组（72%和48%）的存活率相似。基因治疗10周后左室舒张尺寸、射血分数、舒张压无显著差异。两组心脏重量、纤维化程度、tunel阳性心肌细胞百分比、心肌细胞横向大小均无显著差异。综上所述，sFas基因治疗不能抑制UM-X 7.1仓鼠心力衰竭的进展，尽管血清sFas明显增加。这表明Fas-Fas配体系统独立于UM-X 7.1仓鼠扩张型心肌病的进展。

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.