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


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.
Agüero
J
J
Heart Failure and Transplant Unit, Department of Cardiology, La Fe University Hospital, Valencia, Spain. jaimeaguero30@hotmail.com
Almenar
L
L
D'Ocon
P
P
Oliver
E
E
Montó
F
F
Moro
J
J
Castelló
A
A
Rueda
J
J
Martínez-Dolz
L
L
Sánchez-Lazaro
I
I
Montero
J A
JA
D002311:Cardiomyopathy, Dilated / Q000201:enzymology / Q000503:physiopathology / Q000601:surgery*; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics; D054770:G-Protein-Coupled Receptor Kinase 3 / Q000235:genetics; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000235:genetics; D054768:G-Protein-Coupled Receptor Kinases / Q000235:genetics / Q000502:physiology*; D006333:Heart Failure / Q000201:enzymology / Q000503:physiopathology* / Q000601:surgery; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D017202:Myocardial Ischemia / Q000201:enzymology / Q000503:physiopathology / Q000601:surgery*; D011300:Preoperative Care; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D012313:RNA; D054770:G-Protein-Coupled Receptor Kinase 3; C496567:GRK2 protein, human; C517848:GRK3 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2; D054774:G-Protein-Coupled Receptor Kinase 5; D054768:G-Protein-Coupled Receptor Kinases; C517898:GRK5 protein, human