Molecular and structural transition mechanisms in long-term XXXX .

@entity82 @entity712 @entity19 @entity409 @entity22405 @entity1994 @entity460 @entity1284
AIM: We have previously reported that early phase (1   week) of experimental @entity1284 ( @entity1284 ) has an adaptive phenotype while wall stress-matched pressure overload (PO) is maladaptive. Here we investigate the transition from adaptation to @entity712 ( @entity712 ) in long-term @entity1284 . METHODS AND RESULTS: FVB/N wild-type @entity19 were subjected to @entity1284 induced by aortocaval shunt, and were followed by serial echocardiography until in vivo left ventricular ejection fraction was below <50% (135        35   days). @entity712 was evident from increased lung and liver weight and increased mortality compared with sham. Maladaptive remodelling resulted in significantly reduced sarcomeric @entity22405 phosphorylation (causing increased sarcomeric stiffness), whereas @entity82 was not increased. This was paralleled by re-expression of the fetal gene program, activation of @entity460 /calmodulin-dependent protein kinase II (CaMKII), decreased protein kinase B ( @entity1994 ) phosphorylation, high oxidative stress, and increased apoptosis. Consistently, development of @entity712 and mortality were significantly aggravated in @entity1994 -deficient @entity19 . CONCLUSION: Transition to @entity712 in @entity1284 is associated with decreased @entity1994 and increased CaMKII signalling pathways together with increased oxidative stress and apoptosis. Lack of @entity82 together with sarcomeric @entity22405 hypophosphorylation indicates an increased stiffness at the sarcomeric but not matrix level in @entity1284 -induced @entity712 (in contrast to PO). Transition to @entity712 may result from myocyte loss and @entity409 owing to increased stiffness.
