title: In vivo acceleration of heart relaxation performance by parvalbumin gene delivery.
abstract: Defective cardiac muscle relaxation plays a causal role in heart failure. Shown here is the new in vivo application of parvalbumin, a calcium-binding protein that facilitates ultrafast relaxation of specialized skeletal muscles. Parvalbumin is not naturally expressed in the heart. We show that parvalbumin gene transfer to the heart in vivo produces levels of parvalbumin characteristic of fast skeletal muscles, causes a physiologically relevant acceleration of heart relaxation performance in normal hearts, and enhances relaxation performance in an animal model of slowed cardiac muscle relaxation. Parvalbumin may offer the unique potential to correct defective relaxation in energetically compromised failing hearts because the relaxation-enhancement effect of parvalbumin arises from an ATP-independent mechanism. Additionally, parvalbumin gene transfer may provide a new therapeutic approach to correct cellular disturbances in calcium signaling pathways that cause abnormal growth or damage in the heart or other organs.
authors.affiliation: Department of Physiology, Medical School, University of Michigan, Ann Arbor, Michigan 48109-0622, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Szatkowski
authors.forename: M V
authors.initials: MV
authors.lastname: Westfall
authors.forename: C A
authors.initials: CA
authors.lastname: Gomez
authors.forename: P A
authors.initials: PA
authors.lastname: Wahr
authors.forename: D E
authors.initials: DE
authors.lastname: Michele
authors.forename: C
authors.initials: C
authors.lastname: DelloRusso
authors.forename: I I
authors.initials: II
authors.lastname: Turner
authors.forename: K E
authors.initials: KE
authors.lastname: Hong
authors.forename: F P
authors.initials: FP
authors.lastname: Albayya
authors.forename: J M
authors.initials: JM
authors.lastname: Metzger
mesh_terms: D000818:Animals; D004562:Electrocardiography; D005260:Female; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles; D006439:Hemodynamics; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects; D010320:Parvalbumins / Q000235:genetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D010320:Parvalbumins