Suppressed phospholamban levels differentiate irreversibly dysfunctional from hibernating myocardium in humans.
OBJECTIVE
We studied whether dysfunction of human hibernating (HIB) and irreversibly dysfunctional myocardium (IRDM) are associated with altered levels of the sarcoplasmatic reticulum calcium handling proteins Ca2+-ATPase (SERCA2a) and its inhibitor phospholamban (PLB).


METHODS
In 12 patients myocardial biopsies were taken during bypass surgery and analysed for contents of these proteins. We classified regions as control, HIB, or IRDM based on echocardiographic studies before and 6 months after surgery.


RESULTS
SERCA2a content (mean+/-SEM) was similar to control in HIB and IRDM (2.6 +/- 1.7, 3.8 +/- 2.0, and 3.4 +/- 1.9 units/g non-collagen protein (NCP), p = 0.40). PLB content was similar to control in HIB (2.6 +/- 0.4 and 3.5 +/- 0.5 units/microg NCP) but reduced in IRDM (0.9 +/- 0.2 units/microg NCP, p < 0.05). SERCA2a:PLB ratio, an indicator of SERCA2a activity, did not differ between control and HIB (1.2 +/- 0.3 and 1.4 +/- 0.4 units/microg NCP) but was increased in IRDM (5.1 +/- 1.7 units/microg NCP, p < 0.05).


CONCLUSIONS
Inappropriate SERCA2a activity due to suppressed PLB levels may represent a maladaptive mechanism in chronic ischemic myocardium being causally linked to irreversibility of left ventricular dysfunction.
Wiggers
Henrik
H
Department of Cardiology, Skejby Hospital, Aarhus University Hospitals, Aarhus, Denmark. henrikwiggers@dadlnet.dk
Nielsen
Torsten Toftegaard
TT
Vorum
Henrik
H
Honoré
Bent
B
Randsbaek
Flemming
F
Kimose
Hans Henrik
HH
Paulsen
Peter Kildeberg
PK
Bøtker
Hans Erik
HE
D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000032:analysis / Q000378:metabolism*; D016022:Case-Control Studies; D001026:Coronary Artery Bypass / Q000379:methods; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D017682:Myocardial Stunning; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D012494:Sampling Studies; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis; D046509:Tissue Culture Techniques; D000099211:Phospholamban
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban