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

Abstract:

: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 Ca(2+)-cycling proteins and beta-adrenergic receptor density, but the hypertrophied human heart remains largely under studied. 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. beta-adrenergic receptor density was determined by radioligand binding. mRNA for atrial natriuretic factor, calsequestrin, sarcoplasmic reticulum Ca(2+)-ATPase, and phospholamban was measured by Northern blot. Actin, calsequestrin, sarcoplasmic reticulum Ca(2+)-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, beta -adrenergic receptor density and both mRNA and protein levels of the Ca(2+)-ATPase were significantly decreased v non-failing hearts. By comparison, hypertrophied hearts showed a reduction in mRNA expression for both the Ca(2+)-ATPase and phospholamban with no change in the corresponding protein levels, and no change in beta-receptors. These data suggest that the previously demonstrated reduction in beta-adrenergic receptors and Ca(2+)-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.

journal_name

J Mol Cell Cardiol

authors

DiPaola NR,Sweet WE,Stull LB,Francis GS,Schomisch Moravec C

doi

10.1006/jmcc.2001.1390

keywords:

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

1283-95

issue

6

eissn

0022-2828

issn

1095-8584

pii

S0022282801913902

journal_volume

33

pub_type

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