Correlation Between Beta-Adrenoceptors and G-Protein-Coupled Receptor Kinases in Pretransplantation Heart Failure

Introduction. Prolonged catecholamine overstimulation of the myocardium in chronic heart failure causes a reduction in the number and functionality of betal-adrenoceptors (beta 1-AR) of the heart. Desensitization of beta 1-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 beta 1-AR in the myocardiurn 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 beta 1-AR and the isoenzymes GRK2, GRK3, and GRK5. Results. We observed a significant correlation between beta 1-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 beta 1-AR and GRK2 and GRK3 levels. GRK5, the subtype predominantly expressed in the myocardium, showed a lesser correlation with beta 1-AR levels.