title: Diastolic myofilament dysfunction in the failing human heart.
abstract: In recent years, it has become evident that heart failure is not solely due to reduced contractile performance of the heart muscle as impaired relaxation is evident in almost all heart failure patients. In more than half of all heart failure patients, diastolic dysfunction is the major cardiac deficit. These heart failure patients have normal (or preserved) left ventricular ejection fraction, but impaired diastolic function evident from increased left ventricular end-diastolic pressure. Perturbations at the cellular level which cause impaired relaxation of the heart muscle involve changes in Ca(2+)-handling proteins, extracellular matrix components, and myofilament properties. The present review discusses the deficits in myofilament function observed in human heart failure and the most likely underlying causal protein changes. Moreover, the consequences of impaired myofilament function for in vivo diastolic dysfunction are discussed taking into account the reported changes in Ca(2+) handling.
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, van der Boechorststraat 7, 1081 BT, Amsterdam, the Netherlands. j.vandervelden@vumc.nl
authors.forename: Jolanda
authors.initials: J
authors.lastname: van der Velden
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003971:Diastole / Q000502:physiology*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D013599:Systole / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D002118:Calcium