Ca(2+)-transporting ATPase, phospholamban, and calsequestrin levels in nonfailing and failing human myocardium.

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Abstract
BACKGROUND Observations of abnormalities in the diastolic components of intracellular Ca2+ transients in failing human left ventricular myocardium have raised the possibility that reductions in the level or function of sarcoplasmic reticulum proteins involved in Ca2+ transport contribute to the pathophysiology of dilated cardiomyopathy in humans. Functional assays, however, have revealed no differences in ATP-dependent Ca2+ transport or its modulation by phospholamban in sarcoplasmic reticulum-enriched microsomes prepared from nonfailing and failing human left ventricular myocardium. The purpose of the present study was to quantify protein levels of Ca(2+)-transporting ATPase, phospholamban, and calsequestrin directly in nonfailing and failing human left ventricular myocardium. METHOD AND RESULTS Total protein extracts were prepared from nonfailing left ventricular myocardium from the hearts of unmatched organ donors with normal left ventricular contractility (n = 6) and from failing left ventricular myocardium from the excised hearts of transplant recipients with class IV heart failure resulting from idiopathic dilated cardiomyopathy (n = 6). Ca(2+)-transporting ATPase, phospholamban, and calsequestrin contents were determined by quantitative immunoblotting with monoclonal and affinity-purified polyclonal antibodies. The levels of the three proteins were identical in nonfailing and failing human left ventricular myocardium. CONCLUSIONS These results indicate that protein levels of Ca(2+)-transporting ATPase, phospholamban, and calsequestrin are not diminished in failing human left ventricular myocardium and that downregulation of the Ca(2+)-transporting ATPase and phospholamban is not part of the molecular pathophysiology of dilated cardiomyopathy in humans.

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