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Ischemic heart failure enhances endogenous myocardial apelin and APJ receptor expression

Abstract

Apelin interacts with the APJ receptor to enhance inotropy. In heart failure, apelin-APJ coupling may provide a means of enhancing myocardial function. The alterations in apelin and APJ receptor concentrations with ischemic cardiomyopathy are poorly understood. We investigated the compensatory changes in endogenous apelin and APJ levels in the setting of ischemic cardiomyopathy.

Male, Lewis rats underwent LAD ligation and progressed into heart failure over 6 weeks. Corresponding animals underwent sham thoracotomy as control. Six weeks after initial surgery, the animals underwent hemodynamic functional analysis in the presence of exogenous apelin-13 infusion and the hearts were explanted for western blot and enzyme immunoassay analysis.

Western blot analysis of myocardial APJ concentration demonstrated increased APJ receptor protein levels with heart failure (1890750±133500 vs. 901600±143120 intensity units, n=8, p=0.00001). Total apelin protein levels increased with ischemic heart failure as demonstrated by enzyme immunoassay (12.0±4.6 vs. 1.0±1.2 ng/ml, n=5, p=0.006) and western blot (1579400±477733 vs. 943000±157600 intensity units, n=10, p=0.008). Infusion of apelin-13 significantly enhanced myocardial function in sham and failing hearts. We conclude that total myocardial apelin and APJ receptor levels increase in compensation for ischemic cardiomyopathy.

Abbreviations

CHO:

Chinese hamster ovary

DTT:

dithiothreitol

EDTA:

ethylenediaminotetraacetic acid

EIA:

enzyme immunoassay

LAD:

left anterior descending

SDS:

sodium dodecyl sulphate

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Correspondence to Y. Joseph Woo.

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Atluri, P., Morine, K.J., Liao, G.P. et al. Ischemic heart failure enhances endogenous myocardial apelin and APJ receptor expression. Cell Mol Biol Lett 12, 127–138 (2007). https://doi.org/10.2478/s11658-006-0058-7

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  • DOI: https://doi.org/10.2478/s11658-006-0058-7

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