Role of G Protein-Coupled Receptor Kinase 5 in Animal Model of Cardiac Hypertrophy

Sara Alhaidar, Asma Aloneazi, Anfal Bin Dayel, Nouf Alrasheed, Tahani Alshammary, Rehab Ali
King Saud University

Introduction/Background & aims G protein couple receptor kinase 2 and 5 (GRK2 and GRK5) are the main negative regulator for β-adrenoceptor activation [1], which play an important role in cardiac function and contractility. Importantly, up-regulation in GRK2 levels has been found play an important role in cardiac hypertrophy development. GRK5 can act as a class II HDAC kinase in cardiomyocyte nuclei [2]. However, little is known about whether GRK5 modulates isoprenaline induced cardiac hypertrophy and the change in protein level of GRK5 in animal model of cardiac hypertrophy is not well elucidated yet. This research aims to investigate the change in GRK5 protein expression in isoprenaline-induced cardiac hypertrophy animal model.

Method/Summary of work Cardiac hypertrophy was induced in rats by daily Intraperitoneal injection of Isoproterenol (5mg/kg/day). After three weeks, cardiac hypertrophy biomarkers were assessed. GRK5 protein expression were detected using western blotting and immunohistochemistry techniques. Ethics reference number for this study is KSU-SE-20-25.

Results/Discussion ISO treatment significantly increased heart weight to body weight ratio [6.2±0.3 vs. 5.24 ±0.25 (P≤0.05) n≥5], serum creatine kinase MB [2.09±0.9 vs. 1.03±0.19 (P≤0.05) n≥3] and troponin T levels [176.3±31.4 vs. 51.54±13.1 (P≤0.05) n≥3] as compared to control rats. Additionally, histopathological examination of rats exposed to ISO treatment showed enlarged and nuclei and increased collagen fibres indicative of ventricular hypertrophy. ISO treatment produced a significant increase in the expression of myocardial GRK5 by immunoblotting [0.48±0.04 vs. 0.27±0.06 (P≤0.01) n≥8] that were associated with significant increase brown staining in immunohistopathological examination indicative of overexpression of GRK5 as compared to normal rats.

Conclusion(s) Our research yielded promising results verifying a strong link between animal model cardiac hypertrophy and an over expression of GRK5. Our results suggest that over-expression of GRK5 in animal model of cardiac hypertrophy might be harmful to the heart and play an important role in pathological cardiac hypertrophy development. Furthermore, over-expressed GRK5 could be suggested as new marker to investigate cardiac hypertrophy development or as potential therapeutics target.

Reference(s)

1. Hu, L.A., et al., (2002) J Biol Chem, 277(2): p.1607-13.

2. Leineweber, K., et al., (2005) Cardiovascular Research, 66(3): p.512-519.