Suppressed phospholamban levels differentiate irreversibly dysfunctional from hibernating myocardium in humans |
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| Authors: | Henrik Wiggers Torsten Toftegaard Nielsen Henrik Vorum Bent Honoré Flemming Randsbæk Hans Henrik Kimose |
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| Affiliation: | 1. Department of Cardiology, Skejby Hospital, Aarhus University Hospitals, Aarhus, Denmarkhenrikwiggers@dadlnet.dk;3. Department of Cardiology, Skejby Hospital, Aarhus University Hospitals, Aarhus, Denmark;4. Institute of Medical Biochemistry, University of Aarhus, Aarhus, Denmark;5. Department of Thoracic Surgery, Skejby Hospital, Aarhus University Hospitals, Aarhus, Denmark |
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| Abstract: | Objectives 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).Design 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/μg NCP) but reduced in IRDM (0.9±0.2 units/μg 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/μg NCP) but was increased in IRDM (5.1±1.7 units/μg 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. |
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| Keywords: | Contractility heart failure hibernation myocardial stunning phospholamban SERCA2a |
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