Beta-adrenergic receptors and calcium cycling proteins in non-failing, hypertrophied and failing human hearts: Transition from hypertrophy to failure

Left ventricular hypertrophy may lead to heart failure. The transition betw een hypertrophy and heart failure is, however, incompletely understood. On the cellular level. human heart failure is characterized by alterations in Ca2+-cycling proteins and beta -adrenergic receptor density. but the hypert rophied human heart remains largely understudied. In this investigation, 21 donor hearts which could not be used for transplantation were studied. Ten of these hearts came from organ donors with documented left ventricular hy pertrophy and normal cardiac function. Eleven of the hearts were non-failin g, obtained from individuals with no evidence of cardiac disease. Nine fail ing hearts from transplant recipients were also studied. beta -adrenergic r eceptor density was determined by radioligand binding. mRNA for atrial natr iuretic factor, calsequestrin, sarcoplasmic reticulum Ca2+-ATPase, and phos pholamban was measured by Northern blot. Actin, calsequestrin, sarcoplasmic reticulum Ca2+-ATPase, and phospholamban proteins were quantified by Weste rn blot. In both hypertrophied and failing ventricles, mRNA for atrial natr iuretic factor was expressed. as compared to no expression in non-failing h earts. In failing hearts, beta -adrenergic receptor density and both mRNA a nd protein levels of the Ca2+-ATPase were significantly decreased nu non-fa iling hearts. By comparison, hypertrophied hearts showed a reduction in mRN A expression for both the Ca2+-ATPase and phospholamban with no change in t he corresponding protein levels, and no change in beta -receptors. These da ta suggest that the previously demonstrated reduction in beta -adrenergic r eceptors and Ca2+-cycling proteins in the failing human heart may be featur es of the decompensated state, but are not found in human hearts with left ventricular hypertrophy and preserved systolic function. (C) 2001 Academic Press.