Soluble Fas, an inhibitor of apoptosis, gene therapy using adenovirus vector for ischemia-reperfusion injury

我们研究了可溶性Fas （sFas）对梗死后左心室重构和心力衰竭的潜在治疗作用，sFas是一种细胞凋亡抑制剂。在小鼠心肌梗死（MI）第3天，将编码sFas的腺病毒（Ad.CAG-sFas）注射至小鼠后肢肌肉（1 × 10^9 pfu/只），传递sFas基因。采用编码LacZ基因的腺病毒作为对照。sFas基因治疗成功抑制肉芽组织细胞凋亡，导致慢性期（4周后）纤维组织中血管和肌成纤维细胞丰富的“富细胞疤痕组织”。该治疗极大地缓解了梗死后左心室重构（基于超声心动图改善和心脏与体重比降低）和功能障碍（基于血流动力学测量）。这一结果可能暗示了一种新的治疗策略，甚至适用于心肌梗死亚急性期的心衰。

We examined potential therapeutic effects of soluble Fas (sFas), an inhibitor of apoptosis, on post-infarct left ventricular remodeling and heart failure. On the 3rd day of myocardial infarction (MI) of mice, adenovirus encoding sFas (Ad.CAG-sFas) was injected into the hindlimb muscle (1x10^9 pfu/mouse) to deliver sFas gene. As a control, adenovirus encoding LacZ gene was used. The treatment with sFas gene successfully suppressed apoptosis of granulation tissue cells, resulting in "a cell-rich scar tissue" at chronic stage (4 weeks later) in which blood vessels and myofibroblasts were abundant among fibrous tissue. The treatment greatly alleviated post-infarct left ventricular remodeling (based on improved echocardiogram and reduced heart to body weight ratio) and dysfunction (based on hemodynamic measurements). The results may imply a new therapeutic strategy against post-infarct heart failure, which is applicable even at subacute stage of MI.