Human SERCA2a levels correlate inversely with age in senescent human myocardium.
OBJECTIVE
This study sought to characterize functional impairment after simulated ischemia-reperfusion (I/R) or Ca2+ bolus in senescent human myocardium and to determine if age-related alterations in myocardial concentrations of SERCA2a, phospholamban, or calsequestrin participate in senescent myocardial dysfunction.


BACKGROUND
Candidates for elective cardiac interventions are aging, and an association between age and impairment of relaxation has been reported in experimental animals. Function of the sarcoplasmic reticulum resulting in diastolic dysfunction could be dysregulated at the level of cytosolic Ca2+ uptake by SERCA2a, its inhibitory subunit (phospholamban), or at the level of Ca2+ binding by calsequestrin.


METHODS
Human atrial trabeculae from 17 patients (45-75 years old) were suspended in organ baths, field simulated at 1 Hz, and force development was recorded during I/R (45/120 min). Trabeculae from an additional 12 patients (53-73 years 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 I/R or Ca2+ bolus and related to age. SERCA2a, phospholamban, and calsequestrin from 12 patients (39-77 years old) were assessed by immunoblot.


RESULTS
Functional results indicated that maximum +/-dF/dt and tau were prolonged in senescent (>60 years) human myocardium after I/R (p < 0.05). Calcium bolus increased the maximum +/-dF/dt and decreased tau in younger, but not older patients (p < 0.05). SERCA2a and the ratio of SERCA2a to either phospholamban or calsequestrin were decreased in senescent human myocardium (p < 0.05).


CONCLUSIONS
Senescent human myocardium exhibits decreased myocardial SERCA2a content with age, which may, in part, explain impaired myocardial function after either I/R or Ca2+ exposure.
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
B S
BS
Cain
D R
DR
Meldrum
K S
KS
Joo
J F
JF
Wang
X
X
Meng
J C
JC
Cleveland
A
A
Banerjee
A H
AH
Harken
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D015153:Blotting, Western; D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000032:analysis; D000252:Calcium-Transporting ATPases / Q000032:analysis*; D002155:Calsequestrin / Q000032:analysis; D015331:Cohort Studies; D003600:Cytosol / Q000378:metabolism; D003971:Diastole / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006325:Heart Atria; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000737:chemistry* / Q000201:enzymology / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002155:Calsequestrin; D000099211:Phospholamban