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Correlation between beta-adrenoceptors and G-protein-coupled receptor kinases in pretransplantation heart failure
J Agüero1, L Almenar, P D'Ocon
1Heart Failure and Transplant Unit, Department of Cardiology, La Fe University Hospital, Valencia, Spain. jaimeaguero30@hotmail.com
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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