In addition to ID proteins, the cytoskeleton of car-diomyocytes consists of a sarcomeric skeleton (e.g., titin, a-actinin), true cytoskeletal proteins (i.e., intermediate filaments, microtubules, and actin), and membrane-associated proteins (e.g., dystrophin, spec-trin, talin, vinculin) . This complex network stabilizes cellular organelles, maintains cell size and shape, and plays an active role during contraction/relaxation and intracellular signaling [27,28]. The perisarcomer cytoskeleton anchors to the lateral cell membrane in areas called costameres, which are composed of focal adhesion proteins. Therefore, the cytoskeleton responds to the physical and biochemical properties of the extracellular matrix.
Ultrastructural analysis of ARVC/D revealed an irregular or decreased cytoskeleton in the region of the Z band and cell membrane invaginations that form T-tubules (Fig. 6.3), as well as in the perinuclear area in many cardiomyocytes. The lateral costameres in some cells were numerous while in others, with decreased invagination of cell-membrane-forming T-tubules, were single or aggregated in the area of the cell membrane outside of the Z-band region (Fig. 6.3). These were not related to the presence of collagen in the extracellular space. Cytoskeletal alterations have been reported to be responsible for cellular contractile dysfunction [27,29]. It is also known that costameres are responsible for cell structural and functional integrity since they are involved in fixation of sarcomeres to the lateral sarcolemma and stabilization of T-tubules [27, 30]. It is not clear if the varied number of
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