GRK2 Expression in Lymphocytes of Human Patients with Heart Failure-A New Biomarker

Abstract

Introduction: Despite numerous therapeutic advances recently for heart failure (HF), hospitalizations and deaths are still rising. Thus, new treatments as well as improved biomarkers are critically needed to improve the overall care of HF patients. Recently, we have shown that G-protein Coupled Receptor Kinase-2 (GRK2) expression in peripheral lymphocytes tracks with myocardial levels and higher levels in the blood is associated with more severe HF. Hypothesis and Methods: Our hypothesis is that blood GRK2 is a novel biomarker in HF that may help represent a surrogate marker. In order to solidify our previous results showing that lymphocyte GRK2 is negatively associated with LV function in HF, we need to compare levels in HF patients to normal control subjects without LV dysfunction. We have determined lymphocyte GRK2 protein levels in HF and control subjects in this study. HF subjects were recruited and consented during their hospitalization or their outpatient visit to a HF specialist. Patients with normal LV function and taking no cardiovascular medicines were also recruited. Blood was drawn from these subjects and the white blood cells were isolated using Ficoll gradient centrifugation. Purified lymphocyte protein extracts were used for GRK2 protein immunoblotting and quantification via densitometry and normalization with the housekeeping protein, GAPDH. Results: GRK2 levels expressed as a ratio between GRK2 expression and GAPDH (GRK2/GAPDH) in the normal control group (n = 30) was 0.264 ± 0.068. Importantly, in HF patients (n = 20), we found a significant 3-4 fold increase in GRK2 levels in peripheral blood, 1.00 ± 0.258 GRK2/GAPDH (P<0.05). Moreover, there was a relationship between GRK2 levels and disease severity (HF class) in the HF patients. Conclusions: With a larger number of study subjects, we have confirmed that GRK2 in white blood cells is elevated in human patients with failing hearts when compared to subjects with normal LV function. Future studies will compare GRK2 levels in HF patients treated with standard pharmacologic and device therapy to test our hypothesis that GRK2 can be a surrogate marker for determination of a given patient's response to treatment.