title: Functional disturbances due to structural remodeling in the failing human heart.
abstract: In severely hypertrophied hearts structural remodeling occurs continuously and finally leads to heart failure. The remodeling process involves all structural components of the cardiomyocyte and all protein families and it consists of cellular enlargement accompanied by degeneration in addition to the occurrence of fibrosis. Nuclei are increased in size but the nuclear volume/cell volume ratio is reduced. Transcription and translation are downregulated for contractile and sarcomeric skeleton proteins but both are upregulated for cytoskeletal and membrane-associated proteins. The connexin43 content is significantly reduced. Chronic degeneration finally leads to cell death by ubiquitin-related autophagy, and acute ischemic cell death (oncosis) is also observed. Apoptosis seems to be of minor importance. The morphological alterations described here are the structural correlate of the typical clinical characteristics of heart failure in human patients: of reduced contractile function, of increased ventricular stiffness represented by an increased left end-diastolic pressure and of ventricular arrhythmia.
authors.affiliation: Department of Cardiac Surgery, Kerckhoff Clinic, Bad Nauheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hein
authors.forename: A
authors.initials: A
authors.lastname: Elsässer
authors.forename: S
authors.initials: S
authors.lastname: Kostin
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.forename: J
authors.initials: J
authors.lastname: Schaper
mesh_terms: D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002467:Cell Nucleus; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology; D015854:Up-Regulation; D020257:Ventricular Remodeling
chemical_list: D003598:Cytoskeletal Proteins; D008565:Membrane Proteins