title: The cytoskeleton and related proteins in the human failing heart.
abstract: In addition to functional alterations, heart failure has a structural basis as well. This concerns all components of the cardiac myocytes as well as the extracellular space. Proteins of the cardiomyocyte can be subdivided in 5 different categories: 1) Contractile proteins including myosin, actin, tropomyosin and the troponins. 2) Sarcomeric skeleton: titin, myosin binding protein C, alpha-actinin, myomesin, and M-protein. 3) True 'cytoskeletal' proteins: tubulin, desmin and actin. 4) Membrane-associated proteins: dystrophin, spectrin, talin, vinculin, ankyrin and others. 5) Proteins of the intercalated disc: desmosomes consisting of desmoplakin, desmocollin, desmoglein and desmin; adherens junctions with N-cadherin, the catenins and vinculin, and gap junctions with connexin. Failing myocardium obtained from patients undergoing cardiac transplantation exhibits ultrastuctural degeneration and an altered nucleus/cytoplasm relationship. The contractile proteins and those of the sarcomeric skeleton, especially titin, are downregulated, the cytoskeletal proteins desmin and tubulin and membrane-associated proteins such as vinculin and dystrophin are upregulated and those of the intercalated disc are irregularly arranged. Elevation of cytoskeletal proteins correlates well with diastolic and contractile dysfunction in these patients. The enlarged interstitial space contains fibrosis, i.e. accumulations of fibroblasts and extracellular matrix components, in addition to macrophages and microvascular elements. Loss of the contractile machinery and related proteins such as titin and alpha-actinin may be the first and decisive event initiating an adaptive increase in cytoskeleton and membrane associated components. Fibrosis may be stimulated by subcellular degeneration. The hypothesis is put forward that all proteins of the different myocardial compartments contribute to the deterioration of cardiac function in heart failure.
authors.affiliation: Max Planck Institute, Kerckhoff-Clinic, Dept. of Cardiac Surgery, Bad Nauheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kostin
authors.forename: S
authors.initials: S
authors.lastname: Hein
authors.forename: E
authors.initials: E
authors.lastname: Arnon
authors.forename: D
authors.initials: D
authors.lastname: Scholz
authors.forename: J
authors.initials: J
authors.lastname: Schaper
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000473:pathology / Q000503:physiopathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism* / Q000648:ultrastructure*; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D003893:Desmin / Q000378:metabolism / Q000648:ultrastructure; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000648:ultrastructure; D012016:Reference Values; D012680:Sensitivity and Specificity; D014404:Tubulin / Q000378:metabolism / Q000648:ultrastructure; D016596:Vinculin / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D003598:Cytoskeletal Proteins; D003893:Desmin; D014404:Tubulin; D016596:Vinculin