Journal of Molecular Medicine

, Volume 74, Issue 6, pp 321–332 | Cite as

Sarcoplasmic reticulum Ca2+ATPase and phospholamban mRNA and protein levels in end-stage heart failure due to ischemic or dilated cardiomyopathy

  • M. Flesch
  • R. H. G. Schwinger
  • P. Schnabel
  • F. Schiffer
  • I. van Gelder
  • U. Bavendiek
  • M. Südkamp
  • F. Kuhn-Regnier
  • M. Böhm
Original Article
Received:
Accepted:

Abstract

Abnormalities in intracellular Ca2+ handling play a crucial role in the pathogenesis of heart failure. The reduced capacity of failing human myocardium to restore low resting Ca2+ levels during diastole has been explained by the impairment of Ca2+ uptake into the sarcoplasmic reticulum (SR) via the SR Ca2+ATPase. It is unclear whether Ca2+ATPase function, protein levels, and mRNA steady-state levels correspond to one other, and whether the cause of heart failure, namely idiopathic dilated or ischemic cardiomyopathy, produces different changes. The present study examined SR Ca2+ATPase activity and both mRNA and protein levels of SR Ca2+ATPase, phospholamban, and Giα2 in left ventricular myocardium from eight nonfailing hearts, from eight hearts of patients with idiopathic dilated cardiomyopathy (DCM), and from six hearts from patients with ischemic cardiomyopathy (ICM). Compared to nonfailing myocardium, the activity of the SR Ca2+ATPase was significantly reduced in failing myocardium from patients with DCM (36%, P<0.01) and from patients with ICM (37%, P<0.001). Significantly lower levels of SR Ca2+ATPase mRNA levels (55% and -56%, P<0.001 for DCM and ICM, respectively) and phospholamban mRNA (45%, P<0.001 for DCM; 31%, P<0.05 for ICM) were observed in failing than in nonfailing myocardium. In contrast, no significant changes were observed at the level of proteins. Giα2 mRNA and protein levels were both significantly increased in failing mycocardium. There were no differences between idiopathic dilated and ischemic cardiomyopathy concerning the examined parameter. It is concluded that reduced SR Ca2+ATPase activity contributes to an altered intracellular Ca2+ handling by the SR in both dilated and ischemic cardiomyopathic hearts. However, changes in SR Ca2+ATPase and phospholamban steady-state protein levels do not contribute to these alterations. The dissociation between protein and mRNA levels provides evidence for a posttranscriptional or posttranslational regulation of these proteins. The observed alterations are not dependent on the underlying cause of end-stage heart failure.

Key words

Heart failure Human left ventricle Sarcoplasmic reticulum Ca2+ATPase Phospholamban cAMP 

Abbreviations

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

Giα2

Inhibitory G-protein α-subunit

β-MHC

β-Myosin heavy chain

PAGE

Polyacrylamide gel electrophoresis

SDS

Sodium dodecylsulphate

SR

Sarcoplasmic reticulum

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • M. Flesch
    • 1
  • R. H. G. Schwinger
    • 1
  • P. Schnabel
    • 1
  • F. Schiffer
    • 1
  • I. van Gelder
    • 1
  • U. Bavendiek
    • 1
  • M. Südkamp
    • 2
  • F. Kuhn-Regnier
    • 2
  • M. Böhm
    • 1
  1. 1.Klinik III für Innere Medizin, Universität KölnKölnGermany
  2. 2.Klinik für Herz- und Gefässchirurgie Universität KölnKölnGermany

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