G protein-coupled receptor kinase-2: A potential biomarker for early diabetic cardiomyopathy

G protein-coupled receptor kinase-2 (GRK2) has been shown as a key regulator of cardiac function, and the myocardial GRK2 levels are mirrored by the levels in peripheral blood mononuclear cells (PBMCs). In this study, we evaluated the myocardial and PBMCs GRK2 levels in early diabetic cardiomyopathy (DCM).

C57BL/KS-db/db male diabetic mice at 12 weeks of age, as the type 2 diabetes (T2DM) animal model of early DCM were evaluated. Forty-four T2DM patients with left ventricular diastolic dysfunction (LVDD), without evidence of hypertension, coronary artery diseases, congestive heart failure, and diabetic complications and without evidence of ischemia in a maximal treadmill exercise test, were recruited as the DM + LVDD group; 30 age-matched T2DM patients without LVDD were recruited as the DM control group. Left ventricular diastolic function was evaluated by cardiac tissue Doppler. The pseudonormal pattern of ventricular filling and E'/A' < 1 were regarded as LVDD.

Compared to 8-week-old diabetic mice and 12-week-old control mice, GRK2-mRNA level and expression in myocardial tissues of 12-week-old diabetic mice were significantly increased, as well as the left ventricular wall thickness and systolic function. And the collagen volume fraction (CVF), collagen-3 expression, P53 expression, and cell apoptotic rate in the myocardium of 12-week-old diabetic mice elevated as well. The GRK2-mRNA level in PBMCs of DM with LVDD was significantly higher than in DM control without LVDD.

GRK2 expression increased in the myocardial tissue and the PBMCs at the early stage of DCM. These data support further research on the role of GRK2 as the clinical biomarker for early DCM.