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In an early study, it was shown that desmin was increased during the development of hypertrophy, possibly to keep sarcomeres in register. On the other hand, in hypertrophy and failure in feline or canine hearts, the organization and amount of desmin laments were found to be normal. We would like to put forward the concept that all subcellular components of the cardiomyocytes as well as all structural protein families are involved in this process.The primary defect in dilated cardiomyopathy, the phenotype of heart failure discussed here, most probably occurs in the myocyte, either by inammatory, autoimmune or genetic processes causing injury to the aficted cells.Hypertrophy is one typical reaction that upon continuation of progressive damaging processes may nally change into atrophy.Mitochondria react with an increase in number and decrease in size.The cardiomyocyte nuclei enlarge but not to such a degree that a normal nucleuscytoplasm correlation is maintained indicating that a partial exhaustion of transcriptional processes may take place.One of the most important changes is the loss of contractile material and of proteins of the sarcomeric skeleton.A concomitant increase in cytoskeletal proteins tubulin and desmin may be an adaptative mechanism to compensate for the loss of cellular integrity caused by the lack of sarcomeres and their stabilizing proteins, especially titin.A further adaptation to a changing subcellular composition of the cardiomyocytes may be the increase in membrane associated proteins that facilitate interactions with the extracellular milieu as well as the group of intercalated disc proteins.The increase in cytoskeletal and membrane associated proteins accompanied by a loss of contractile laments and sarcomeric skeleton components may be regarded as the morphological basis of contractile and diastolic dysfunction in failing hearts.Extracellularmatrix rigidity causes strengthening of integrincytoskeleton linkages.Kinesin is a candidate for crossbridging microtubules and intermediate laments.View publication stats View publication stats The user has requested enhancement of the downloaded file.This immense variation in cell shape depends on an underlying network of dynamic and interconnected actin and microtubule polymers.The glomerular podocyte is an archetypal example of such specialization, with a complex cytoskeleton underlying its delicate architectural features.Dynamic control of this cytoskeletal matrix seems to center around the slit diaphragm, a complex of proteins at the cellcell junction between adjacent podocyte foot processes.This junction includes molecules that are unique to the podocyte that probably determine the correct morphology of the cell, and are targets of disease processes that disrupt the intricate balance of signaling that controls the cytoskeletal matrix.Our understanding of the cellular basis of proteinur ia has improved dramat Nilotinib ically in the past years, including elucidation of the properties of the cel lu lar components of the GFB and the coordinated interactions between the cell types present in the GFB.The study of these cells has revealed many novel facets of glomerular disease.The functions that podocytes need to Fluphenazine hydrochloride fulfill determine many of the specialized features of this cell, and also reveal cellspecific targets for disease pathogenesis, from diabetic nephropathy to the idiopathic nephrotic syndromes.For example, in order to withstand high pressure in the capillaries, the podocyte must possess a dynamic contractile apparatus, and to maintain intact and exact filtration properties, particularly if the cell is also motile, the arrangement of the cyto skeleton needs to be precisely and temporally controlled.

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