HUMAN SERCA2A LEVELS CORRELATE INVERSELY WITH AGE IN SENESCENT HUMAN MYOCARDIUM

Objectives. This study sought to characterize functional impairment af ter simulated ischemia-reperfusion (I/R) or Ca2+ bolus in senescent hu man myocardium and to determine if age-related alterations in myocardi al concentrations of SERCA2a, phospholamban, or calsequestrin particip ate in senescent myocardial dysfunction. Background. Candidates for el ective cardiac interventions are aging, and an association between age and impairment of relaxation has been reported in experimental animal s. Function of the sarcoplasmic reticulum resulting in diastolic dysfu nction could be dysregulated at the level of cytosolic Ca2(+) uptake b y SERCA2a, its inhibitory subunit (phospholamban), or at the level of Ca2+ binding by calsequestrin. Methods. Human atrial trabeculae from 1 7 patients (45-75 years old) were suspended in organ baths, field simu lated at 1 Hz, and force development was recorded during I/R (45/120 m in). Trabeculae from an additional 12 patients (53-73 Sears old) were exposed to Ca2+ bolus (2-3 mmol/L bath concentration). Maximum +/- dF/ dt and the time constant of force decay (tau) were measured before and after UR or Ca2+ bolus and related to age. SERCA2a, phospholamban, an d calsequestrin from 12 patients (39-77 years old) were assessed by im munoblot. Results. Functional results indicated that maximum +/- dF/dt and tau were prolonged in senescent (>60 years) human myocardium afte r I/R (p < 0.05). Calcium bolus increased the maximum +/- dF/dt and de creased tau in younger, but not older patients (p < 0.05), SERCA2a and the ratio of SERCA2a to either phospholamban or calsequestrin were de creased in senescent human myocardium (p < 0.05). Conclusions. Senesce nt human myocardium exhibits decreased myocardial SERCA2a content with age, which may, in part, explain impaired myocardial function after e ither VR or Ca2+ exposure.