title: Suppressed phospholamban levels differentiate irreversibly dysfunctional from hibernating myocardium in humans.
abstract: 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.
authors.affiliation: Department of Cardiology, Skejby Hospital, Aarhus University Hospitals, Aarhus, Denmark. henrikwiggers@dadlnet.dk
authors.forename: Henrik
authors.initials: H
authors.lastname: Wiggers
authors.forename: Torsten Toftegaard
authors.initials: TT
authors.lastname: Nielsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Vorum
authors.forename: Bent
authors.initials: B
authors.lastname: Honoré
authors.forename: Flemming
authors.initials: F
authors.lastname: Randsbaek
authors.forename: Hans Henrik
authors.initials: HH
authors.lastname: Kimose
authors.forename: Peter Kildeberg
authors.initials: PK
authors.lastname: Paulsen
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
mesh_terms: 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
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban