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. 2008 Nov;40(9):3014-6.
doi: 10.1016/j.transproceed.2008.09.011.

Correlation between beta-adrenoceptors and G-protein-coupled receptor kinases in pretransplantation heart failure

J Agüero  1 , L Almenar, P D'Ocon, E Oliver, F Montó, J Moro, A Castelló, J Rueda, L Martínez-Dolz, I Sánchez-Lazaro, J A Montero
Affiliations

Correlation between beta-adrenoceptors and G-protein-coupled receptor kinases in pretransplantation heart failure

J Agüero et al. Transplant Proc. 2008 Nov.

Abstract

Introduction: Prolonged catecholamine overstimulation of the myocardium in chronic heart failure causes a reduction in the number and functionality of beta1-adrenoceptors (beta1-AR) of the heart. Desensitization of beta1-AR is mediated by their phosphorylation by a group of cytosolic kinases (G-protein-coupled receptor kinases GRK). In advanced heart failure, an increase in GRK levels associated with the severity of the disease has been observed.

Objective: The objective of this study was to analyze messenger RNA (mRNA) levels of beta1-AR in the myocardium of patients who underwent transplantation for advanced heart failure and their correlation with expression of the major cardiac isoenzymes of GRK.

Materials and methods: Myocardial tissue samples were obtained from the left ventricles of 14 explanted hearts of patients who underwent transplantation for dilated (n = 7) and ischemic (n = 7) cardiomyopathy. RT-PCR techniques were used to analyze mRNA levels of beta1-AR and the isoenzymes GRK2, GRK3, and GRK5.

Results: We observed a significant correlation between beta1-AR and the 3 subtypes of GRK (R(2) = 0.668, 0.71, and 0.318, respectively).

Conclusions: In patients with advanced heart failure pretransplantation, we observed a significant correlation between beta1-AR and GRK2 and GRK3 levels. GRK5, the subtype predominantly expressed in the myocardium, showed a lesser correlation with beta1-AR levels.

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