title: Thin filament remodeling in failing myocardium.
abstract: While the remodeling process in myocardial failure involves changes in ventricular structure and performance, it is now appreciated that it is also associated with changes in thin filament composition and function. As is discussed, changes at the level thick filament may affect thin filament activation in heart failure. Alterations in actin, troponin and tropomyosin isoform composition do not appear to be significant factors in human heart failure. In contrast, proteolytic degradation of troponin subunits are likely to be playing a functional role in some forms of cardiomyopathy (e.g. ischemic). Finally, phosphorylation of troponin I and troponin T by kinases (most notably protein kinase C) substantially affect thin filament function in failing human myocardium. These findings indicate that functional deficits in thin filament function in failing myocardium are largely reversible and create the potential for future targeted therapies in the treatment of this deadly disease.
authors.affiliation: Department of Medicine, College of Medicine, University of Vermont, VT 05405, USA. vanburen@physiology.med.uvm.edu
authors.forename: Peter
authors.initials: P
authors.lastname: VanBuren
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okada
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000502:physiology*; D000199:Actins / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology; D012333:RNA, Messenger; D014336:Troponin / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D000199:Actins; D020033:Protein Isoforms; D012333:RNA, Messenger; D014336:Troponin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C