The contractile apparatus of cardiomyocytes is considered to be a stable system. However, it undergoes strong rearrangements during heart development as cells progress from their non-muscle precursors. Long-term culturing of mature cardiomyocytes is also accompanied by the reorganization of their contractile apparatus with the conversion of typical myofibrils into structures of non-muscle type. Processes of heart development as well as cell adaptation to culture conditions in cardiomyocytes both involve extracellular matrix changes, which appear to be crucial for the maturation of contractile apparatus. The aim of this review is to analyze the role of extracellular matrix in the regulation of contractile system dynamics in cardiomyocytes. Here, the remodeling of actin contractile structures and the expression of actin isoforms in cardiomyocytes during differentiation and adaptation to the culture system are described along with the extracellular matrix alterations. The data supporting the regulation of actin dynamics by extracellular matrix are highlighted and the possible mechanisms of such regulation are discussed.
Matrix metalloproteinases (MMPs) are implicated in many physiological and pathological processes, including contraction, migration, differentiation, and proliferation. These processes all involve cell phenotype changes, known to be accompanied by reorganization of actin cytoskeleton. Growing evidence indicates a correlation between MMP activity and the dynamics of actin system, suggesting their mutual regulation. Here, data on the influence of MMPs on the actin microfilament system, on the one hand, and the dependence of MMP expression and activation on the organization of actin structures, on the other hand, are reviewed. The different mechanisms of putative actin-MMP regulation are discussed.
Cardiomyocytes in culture undergo reversible rearrangement of their contractile apparatus with the conversion of typical myofibrils into the structures of non-muscle type and the loss of contractility. Along with these transformations, the cardiomyocytes gain the capacity to synthesize extracellular matrix. Here we show that during cultivation of rat neonatal cardiomyocytes, the inherent α-cardiac actin isoform is transiently replaced by α-smooth-muscle actin, whose expression is accompanied by transformation of myofibrils into stress-fiber-like structures. The following down-regulation of α-smooth muscle actin parallels restoration of myofibrillar system and correlates with the accumulation of extracellular collagen and laminin, initially missing from the cardiomyocytes culture.
The highly organized contractile apparatus of cardiomyocytes in heart tissue allows for their continuous contractility, whereas extracellular matrix components are synthesized and spatially organized by fibroblasts and endothelial cells. However, reorganization of the cardiomyocyte contractile apparatus occurs upon their 2D cultivation, which is accompanied by transient loss of their contractility and acquired capability of extracellular matrix synthesis (Bildyug, N. B., and Pinaev, G. P. (2013) Tsitologiya, 55, 713-724). In this study, matrix metalloproteinases were investigated at different times of cardiomyocyte 2D cultivation and 3D cultivation in collagen gels. It was found that cardiomyocytes in 2D culture synthesize matrix metalloproteinases MMP-2 and MMP-9, wherein their amount varies with the cultivation time. The peak MMP-9 amount is at early cultivation time, when the reorganization of cardiomyocyte contractile apparatus occurs, and the MMP-2 peak precedes the recovery of the initial organization of their contractile apparatus. Upon cardiomyocyte cultivation in 3D collagen gels, in which case their contractile apparatus does not rearrange, a steady small amount of MMP-2 and MMP-9 is observed. These data indicate that the cardiomyocyte contractile apparatus reorganization in culture is associated with synthesis and spatial organization of their own extracellular matrix.
Heart growth and pathological changes are accompanied by extracellular matrix-dependent alterations in integrins and integrin-associated proteins, suggesting their role in heart development and disease. Most of our knowledge on the involvement of integrins in heart pathology is provided by the in vivo experiments, including cardiac hypertrophy models. However, in vivo studies are limited by the complex organization of heart tissue and fail to discern cell types and particular integrins implicated in hypertrophic signalling. This problem is being addressed by isolated cardiomyocyte primary cultures, which have been successfully used in different in vitro disease models. This review aimed to analyse the general approaches to studying integrins and integrin-associated signalling pathways in cardiac hypertrophy focusing on the in vitro systems. The lessons learned from culture experiments on the models of hypertrophy induced by stretch, stimulating factors, and/or extracellular matrix components are summarized, demonstrating the major involvement of integrin-mediated signalling in cardiac hypertrophic response and its apparent crosstalk with signal pathways induced by stretch or hypertrophy stimulating factors. The benefits and perspectives of using cardiomyocyte primary culture as a hypertrophy model are discussed.
Damage to the hyaline layer of the articular surface is an urgent problem for millions of people around the world. At present, a large number of experimental methods are being developed to address this problem, including the transplantation of a cell-engineered construct (CEC) composed of a biodegradable scaffold with a premixed cell culture into the damaged area of the articular surface. However, current methods for analyzing the effectiveness of such CECs have significant limitations. This study aimed to compare the SEM technique, classical histology, and cryosectioning for the analysis of CECs transplanted to hyaline cartilage.
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