Abstract

BackgroundG 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).MethodsC57BL/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.ResultsCompared 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.ConclusionsGRK2 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.

Highlights

  • Type 2 diabetes (T2DM) is a serious worldwide health problem with a striking increase in prevalence and incidence

  • G protein-coupled receptor kinase-2 (GRK2)-mRNA level was significantly elevated in 12-weekold diabetic mice compared to the 12-week-old control group and elevated in 8-week-old diabetic mice compared to the 8-week-old control group; the difference was not statistically significant (Figure 4); so as for the GRK2 expression in the left ventricular myocardium of mice evaluated by the immunofluorescence assay (Figure 5)

  • The results showed a significant increase in GRK2 expression in myocardial tissue of diabetic mice at 12 weeks of age along with increases of cardiomyocyte apoptosis and myocardial fibrosis and ventricular wall thickening, which can be considered as the early stage of diabetic cardiomyopathy (DCM).[27,28]

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Summary

| INTRODUCTION

Type 2 diabetes (T2DM) is a serious worldwide health problem with a striking increase in prevalence and incidence. Accumulating evidence suggests that left ventricular diastolic dysfunction (LVDD) is the earliest clinical manifestation of DCM, and LVDD implies cardiac tissue remodeling. Poirier and his colleagues found that about 60% of T2DM patients without hypertension and cardiovascular diseases were found with LVDD by cardiac tissue Doppler. Our previous observational study demonstrated that GRK2 expression increased in lymphocytes of T2DM patients without evidence of hypertension and coronary artery diseases.[14]. Db/db mouse is a model of T2DM with leptin receptor insensitivity characterized by significant obesity, fasting hyperglycemia, hyperinsulinemia, and insulin resistance It develops changes in cardiac structure and function similar to those in T2DM patients.[16]. We aimed to investigate the association of GRK2 with early DCM by estimating the expression of GRKs both in the myocardium of diabetic mice and in the PBMCs of patients with early DCM

| MATERIALS AND METHODS
| RESULTS
12 W Control 5
| DISCUSSION
Findings
CONFLICT OF INTEREST
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