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 between hypertrophy and heart failure is, however, incompletely understood. On the cellular level, human heart failure is characterized by alterations in Ca²⁺-cycling proteins and β-adrenergic receptor density, but the hypertrophied 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 hypertrophy and normal cardiac function. Eleven of the hearts were non-failing, obtained from individuals with no evidence of cardiac disease. Nine failing hearts from transplant recipients were also studied. β-adrenergic receptor density was determined by radioligand binding, mRNA for atrial natriuretic factor, calsequestrin, sarcoplasmic reticulum Ca²⁺-ATPase, and phospholamban was measured by Northern blot. Actin, calsequestrin, sarcoplasmic reticulum Ca²⁺-ATPase, and phospholamban proteins were quantified by Western blot. In both hypertrophied and failing ventricles. mRNA for atrial natriuretic factor was expressed, as compared to no expression in non-failing hearts. In failing hearts, β-adrenergic receptor density and both mRNA and protein levels of the Ca²⁺-ATPase were significantly decreased v non-failing hearts. By comparison, hypertrophied hearts showed a reduction in mRNA expression for both the Ca²⁺-ATPase and phospholamban with no change in the corresponding protein levels, and no change in β-receptors. These data suggest that the previously demonstrated reduction in β-adrenergic receptors and Ca²⁺-cycling proteins in the failing human heart may be features of the decompensated state, but are not found in human hearts with left ventricular hypertrophy and preserved systolic function.