Thorac Cardiovasc Surg 2013; 61 - OP254
DOI: 10.1055/s-0032-1332493

Mechanical unloading of the rat heart involves marked changes in the protein kinase-phosphatase balance

AP Schwoerer 1, C Neuber 2, AM Bernhardt 3, A Schmechel 2, G Mearini 2, P Boknik 4, U Kirchhefer 4, W Schmitz 4, H Ehmke 1, T Eschenhagen 2, H Reichenspurner 3, A El-Armouche 5
  • 1Universitätsklinikum Hamburg Eppendorf, Institut für Zelluläre und Integrative Physiologie, Hamburg, Germany
  • 2Universitätsklinikum Hamburg Eppendorf, Institut für Experimentelle Pharmakologie, Hamburg, Germany
  • 3Universitäres Herzzentrum Hamburg, Herz- und Gefäßchirurgie, Hamburg, Germany
  • 4Universität Münster, Institut für Pharmakologie und Toxikologie, Münster, Germany
  • 5Herzzentrum Göttingen, Abteilung für Pharmokologie, Göttingen, Germany

Objectives: Mechanical unloading of failing hearts by left ventricular (LV) assist devices is regularly used as a bridge to transplantation and may lead to symptomatic improvement. The latter has been associated with altered phosphorylation of cardiac regulatory proteins, but the underlying mechanisms remained unknown.

Methods: Here, we tested whether cardiac unloading alters protein phosphorylation by affecting the corresponding kinase- phosphatase balance. Cardiac unloading and reduction in LV mass were induced by heterotopic heart trans- plantation in rats for two weeks (n = 8). Native in situ hearts from the recipient animals were used as controls (n = 8).

Results: The steady-state protein kinase A (PKA) and/or Ca2+-calmodulin-dependent protein kinase II (CaMKII) phosphorylation levels of phospholamban (PLB, Ser16 and Thr17) and troponin I (TnI, Ser23/24) were decreased by 40 – 60% in unloaded hearts. Consistently, in these hearts PKA activity was decreased by ˜80% and the activity of protein phosphatase 1 and 2A was increased by 50% and 90%, respectively. In contrast, CaMKII activity was ˜ 60% higher, which may serve as a partial compensation.

Conclusion: These data indicate that unloading shifts the kinase- phosphatase balance towards net dephosphorylation of PLB and TnI. This shift may also contribute to the reduction in phosphorylation levels of cardiac phosphoproteins observed in diseased human hearts after LVAD.