Apoptosis repressor with caspase recruitment domain is required for cardioprotection in response to biomechanical and XXXX stress.

@entity1 @entity712 @entity296 @entity63 @entity16888 @entity19 @entity1184 @entity741 @entity299 @entity583 @entity393 @entity204
BACKGROUND: @entity741 and @entity712 are associated with an @entity393 due to apoptosis. Whether cardiomyocyte apoptosis plays a causal role in the pathogenesis of @entity712 remains enigmatic. The apoptosis repressor with caspase recruitment domain ( @entity16888 ) is a recently discovered antiapoptotic factor with a highly specific expression pattern in striated muscle and neurons. @entity16888 is a master regulator of @entity204 signaling because it is the only known factor that specifically inhibits both the intrinsic and extrinsic apoptotic death pathway. In this study we attempted to elucidate the physiological role of @entity16888 and to understand pathophysiological consequences resulting from its deletion. METHODS AND RESULTS: We generated @entity16888 @entity19 , which developed normally to adulthood and had no abnormality in cardiac morphology and function under resting conditions. On biomechanical stress induced by aortic banding, @entity16888 @entity19 developed accelerated @entity296 compared with littermate controls, which was characterized by reduced contractile function, @entity299 , and @entity296 . Likewise, @entity63 /reperfusion injury of @entity16888 @entity19 resulted in markedly increased @entity583 sizes. Although in both instances a significant increase in apoptotic cardiomyocytes could be observed in @entity16888 @entity19 , neither in vitro nor in vivo studies revealed any effect of @entity16888 on classic @entity1184 cardiomyocyte growth responses. The pathophysiological relevance of downregulated @entity16888 levels was underscored by specimens from failing @entity1 hearts showing markedly reduced @entity16888 protein levels. CONCLUSIONS: Our study identifies a tissue-specific antiapoptotic factor that is downregulated in @entity1 failing myocardium and that is required for cardioprotection in pressure overload and @entity63 .
