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

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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.