Martin M Lewinter1, Peter Vanburen. 1. Cardiology Unit and the Vermont Heart Failure Research Group, University of Vermont College of Medicine, Burlington, Vermont, USA.
Abstract
BACKGROUND: Myocardial failure is associated with complex, pleiotropic responses involving multiple signaling mechanisms and alterations in structure-function relationships. Myofilament proteins are a central component of these responses and may be modified in various ways, including isoform variation, phosphorylation, and degradation. METHODS AND RESULTS: We have modeled the transition from compensated hypertrophy to failure using a combination of isolated heart and in vitro motility methods in the Dahl salt sensitive rat model. CONCLUSIONS: Our results and prior data indicate that myosin isoform switching probably does not have major functional consequences in failing human myocardium. In contrast, a defect in the thin filament appears to play an important role in the Dahl rat and possibly in patients. The mechanism is uncertain, but preliminary data suggest altered phosphorylation of troponin I and/or T.
BACKGROUND:Myocardial failure is associated with complex, pleiotropic responses involving multiple signaling mechanisms and alterations in structure-function relationships. Myofilament proteins are a central component of these responses and may be modified in various ways, including isoform variation, phosphorylation, and degradation. METHODS AND RESULTS: We have modeled the transition from compensated hypertrophy to failure using a combination of isolated heart and in vitro motility methods in the Dahl salt sensitive rat model. CONCLUSIONS: Our results and prior data indicate that myosin isoform switching probably does not have major functional consequences in failing human myocardium. In contrast, a defect in the thin filament appears to play an important role in the Dahl rat and possibly in patients. The mechanism is uncertain, but preliminary data suggest altered phosphorylation of troponin I and/or T.
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