Lymphocytes a surrogate for monitoring cardiac GRK2 in human heart failure

Researchers have found expression and activity of myocardial G protein-coupled receptor kinase-2 (GRK2) to be mirrored by lymphocyte levels of this kinase, thus providing a surrogate for monitoring cardiac GRK2 in human heart failure (HF).The GRK2 regulates b-adrenergic receptors (b-ARs) in the heart, and its cardiac expression is elevated in human HF. The relevance of the molecular abnormalities of b-AR signalling to the course and pathogenesis of human HF outcome is not well understood. One important aspect of b-AR signalling is that properties of the system in circulating white blood cells appear to mirror those seen in solid tissue. Consequently, many reports have used the lymphocyte system to study b-AR signalling, the results of which have been extrapolated to the cardiac b-AR system. Thus, lymphocytes represent a valuable marker of the functional state of cardiac b-AR signalling, which may also apply to GRK2 regulation.Iaccarino et al. investigated whether myocardial levels and activity of GRK2 levels could be monitored using white blood cells, and whether GRK2 levels in myocardium and lymphocytes may be associated with b-AR dysfunction and HF severity.Two separate study groups were studied; the first consisting of 24 patients undergoing cardiac transplant due to severe deterioration of cardiac function, and the second consisting of 58 patients consecutively admitted into the intensive care coronary unit with a cardiovascular condition positing threat to survival. Left ventricular (LV) specimens of the explanted hearts from the first group of patients were obtained, and blood and lymphocyte samples were obtained from 10 patients in the second group undergoing elective cardiac surgery.Myocardial biopsies from the explanted hearts revealed GRK activity was inversely correlated with b-AR-mediated cyclic-AMP production (R²=-0.215, pppThree key findings emerged from this study. These were:...