The enhanced contractility of the phospholamban-deficient mouse heart persists with aging

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.