Mechanotransduction in Cardiac Remodeling and Heart Failure

Mechanotransduction is the process by which the cells of the heart convert mechanical signals to chemical signals responsible for cellular adaptation and remodeling. When this system cannot meet the demands of increased loading conditions, the cellular response will not be adequate, and eventually the pumping function of the heart will fail. Mechanical signaling and force transmission within and outside the myocyte are important players in the mechanotransduction process, and the cytoskeleton is a key component in the structural link between the force-generating sarcomere, the cell membrane and putative intra-cellular stress-sensing components. Several defects in cytoskeletal components have been linked to cardiac dilation and heart failure. LIM proteins are one such structural component of the cytoskeleton, and defects in these proteins lead to both right and left ventricular dysfunction. Although these proteins may have chemical signaling roles in mechanotransduction, their structural role in force transmission and mechanical signaling is being investigated and characterized. Thus, there is evidence that structural components of the myocardium such as the myocyte cytoskeleton play a critical role in mechanotransduction and are part of the mechanism behind cardiac remodeling and eventual heart failure.

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