Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress

Biomechanical stress is a major stimulus for cardiac hypertrophy and the tr ansition to heart failure. By generating mice that harbor a ventricular res tricted knockout of the gp130 cytokine receptor via Cre-loxP-mediated recom bination, we demonstrate a critical role for a gp130-dependent myocyte surv ival pathway in the transition to heart failure. Such conditional mutant mi ce have normal cardiac structure and function, but during aortic pressure o verload, these mice display rapid onset of dilated cardiomyopathy and massi ve induction of myocyte apoptosis versus the control mice that exhibit comp ensatory hypertrophy. Thus, cardiac myocyte apoptosis is a critical point i n the transition between compensatory cardiac hypertrophy and heart failure . gp130-dependent cytokines may represent a novel therapeutic strategy for preventing in vivo heart failure.