title: The enhanced contractility of the phospholamban-deficient mouse heart persists with aging.
abstract: J. P. Slack, I. L. Grupp, R. Dash, D. Holder, A. Schmidt, M. J. Gerst, T. Tamura, C. Tilgmann, P. F. James, R. Johnson, A. M. Gerdes and E. G. Kranias. The Enhanced Contractility of the Phospholamban-deficient Mouse Heart Persists with Aging. Journal of Molecular and Cellular Cardiology (2001) 33, 1031-1040. Phospholamban ablation in the mouse is associated with significant increases in cardiac contractility. To determine whether this hyperdynamic function persists through the aging process, a longitudinal examination of age-matched phospholamban-deficient and wild-type mice was employed. Kaplan-Meier survival curves indicated no significant differences between phospholamban-deficient and wild-type mice over the first year. Examination of cardiac function revealed significant increases in the rates of contraction (+dP/dt) and relaxation (-dP/dt) in phospholamban-deficient hearts compared with their wild-type counterparts at 3, 6, 12, 18 and 24 months of age. Quantitative immunoblotting indicated that the expression levels of the sarcoplasmic reticulum Ca(2+)-ATPase were not altered in wild-type hearts, while they were significantly decreased at 12 months (40%) and 18 months (20%) in phospholamban-deficient hearts. These findings on the persistence of hyperdynamic cardiac function over the long term suggest that phospholamban may constitute an important target for treatment in heart disease.
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, 231 Bethesda Ave., Cincinnati, OH 45267, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Slack
authors.forename: I L
authors.initials: IL
authors.lastname: Grupp
authors.forename: R
authors.initials: R
authors.lastname: Dash
authors.forename: D
authors.initials: D
authors.lastname: Holder
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: M J
authors.initials: MJ
authors.lastname: Gerst
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: C
authors.initials: C
authors.lastname: Tilgmann
authors.forename: P F
authors.initials: PF
authors.lastname: James
authors.forename: R
authors.initials: R
authors.lastname: Johnson
authors.forename: A M
authors.initials: AM
authors.lastname: Gerdes
authors.forename: E G
authors.initials: EG
authors.lastname: Kranias
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D004452:Echocardiography; D005260:Female; D005838:Genotype; D006321:Heart / Q000502:physiology*; D015151:Immunoblotting; D008297:Male; D051379:Mice; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D013997:Time Factors; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D000099211:Phospholamban