Molecular mechanisms of sarcomere dysfunction in dilated and XXXX .

@entity1184 @entity384 @entity10484 @entity3999 @entity74 @entity460 @entity1121
The sarcomeres form the molecular motor of the cardiomyocyte and consist of a complex multi-protein of thick and thin filaments which are anchored to the cytoskeleton. The thick filament, composed of @entity3999 and associated proteins, and the thin filament composed of actin, tropomyosin and the troponins develop actinmyosin crossbridges which cycle in response to @entity460 resulting in sliding of the filaments and contraction. The thin filament in fixed to the cardiomyocyte cytoskeleton at the Z-disc, a complex of structural and regulatory proteins. A giant protein, @entity10484 , provides an external scaffold and regulates passive force in diastole. Both @entity74 and acquired conditions may affect proteins of the sarcomere. @entity74 of the thick and thin filament proteins are the predominant cause of @entity1121 . These mutations lead to abnormal sarcomere function, often an enhanced sensitivity to @entity460 , and impaired relaxation. This may result in secondary changes in @entity460 cycling and amplification of @entity1184 signaling cascades. Correcting the abnormal function of the sarcomere as well as intervening in later stages of the pathophysiologic cascades may ameliorate disease. In dilated @entity74 in the sarcomere, Z-disc, @entity460 regulatory and cytoskeletal proteins as well as the dystrophin complex may be causal for disease. In @entity384 , disturbances in post-translational modifications of the sarcomere my also play a prominent role. Experimental models indicate that altered phosphorylation of sarcomeric proteins may impair systolic and diastolic function as well as the response to heart rate and afterload. Thus correcting these post-translational changes are legitimate targets for future therapeutic strategies for @entity384 .
