G Protein-Coupled Receptor Kinase 5; A Potential Marker and Possible Therapeutic Target for Cardiac Hypertrophy

Background: G protein coupled receptor kinase 5 (GRK5) exerts a negative regulatory function for β-adrenoceptor activation, which plays an important role in cardiac function and contractility. Importantly, GRK5 expression has been found to play an important role in pathological cardiac disease development. However, the endogenous GRK5 gene expression and the change in its protein level in an animal model of cardiac hypertrophy (CH) is not well elucidated yet. The current study aimed to investigate the change in endogenous GRK5 expression in cardiac myocytes and peripherally circulated lymphocytes using an isoproterenol (ISO) induced cardiac hypertrophy (CH) animal model.Methods: CH was induced in rats by daily intraperitoneal injection of ISO (5mg/kg/day) for 21 days. CH biomarkers were assessed. GRK5 mRNA gene expression in cardiac myocytes and peripherally isolated lymphocytes were assessed by qPCR. Protein expressions were detected using western blotting and immunohistochemistry techniques. Ethics reference number for this study is KSU-SE-20-25.Key findings: ISO-induced CH was confirmed by a marked increase in heart weight to body weight ratio, serum creatine kinase MB, and troponin-T levels associated with histopathological changes. ISO treatment produced a significant increase in mRNA gene expression and protein levels of myocardial GRK5. Moreover, GRK5 mRNA gene expression was elevated in circulating lymphocytes in hypertrophic rats.Conclusions: Ultimate findings indicated that ISO had a meaningful effect on increasing endogenous GRK5 in hypertrophic myocardium. Results reveal that upregulation of GRK5 might play an important role in pathological CH development, suggesting GRK5 as a potential therapeutics target. Furthermore, over-expressed GRK5 in circulating lymphocytes gives the possibility for using of GRK5 gene expression in lymphocytes as a biomarker for CH development.