Myocardial and Peripheral Lymphocytic Transcriptomic Dissociation of β-adrenoceptors and G Protein–coupled Receptor Kinases in Heart Transplantation

Abstract

The genetic expression of adrenergic receptors plays an important pathophysiologic role in heart failure. G protein-coupled receptor kinases (GRKs) desensitize the beta-receptor to catecholaminergic stimulation. It has been suggested that their mRNA expression in peripheral lymphocytes could mirror the changes in their myocardial expression in the failing heart, but this relationship between the myocyte and lymphocyte has not been studied in heart transplantation (HT). The objective of this study was to analyze adrenergic receptor and GRK mRNA expression in myocardium and lymphocytes and their correlation. Twenty-three HT patients without evidence of acute rejection or echocardiographic dysfunction were assessed. Myocardial biopsy samples and peripheral blood lymphocytes were obtained, and alpha(1)- and beta-adrenoceptor subtype and GRK subtype mRNA was analyzed using reverse transcript-polymerase chain reaction (RT-PCR). Mean age was 45 +/- 15 years, with a median of time since HT of 205 (351) days. In biopsies, the beta(1)/beta(2)-adrenoceptor ratio was 57%/42%, and GRK5 was the most commonly expressed, followed by GRK2. In lymphocytes, the beta(1)/beta(2) ratio was 3%/96%, whereas GRK2 mRNA expression was greater than that of other subtypes. There was no correlation between myocardial and lymphocyte parameters. There were no correlations with clinical variables, but lymphocyte beta(2) and GRK2 were increased with time since HT. In the transplanted heart, there is no correlation between mRNA expression of adrenoceptors and GRKs in myocardium and peripheral lymphocytes. With time since transplant, mRNA expression of lymphocyte but not myocardial beta(2)-adrenoceptor and GRK2 increases. Therefore, this dissociation between myocardial and lymphocyte mRNA expression limits the potential use of peripheral blood samples for diagnosis of graft dysfunction.