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

Abstract：

BACKGROUND: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). METHODS: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. RESULTS: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. CONCLUSIONS: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. :背景: 研究显示G蛋白偶联受体激酶2(GRK2)是调节心脏功能的关键因子, 而心肌GRK2的表达水平与外周血单核细胞(PBMC)的GRK2表达存在一致性。本研究评估了早期糖尿病性心肌病(DCM)PBMC的GRK2水平。方法: 动物研究以12周龄的C57BL/KS-db/db雄性糖尿病小鼠作为早期DCM的2型糖尿病(T2DM)研究模型。人群研究中招募了44位T2DM伴有左心室舒张功能障碍(LVDD)的患者为DM + LVDD组, 他们均排除了高血压、冠状动脉疾病、充血性心力衰竭和糖尿病并发症等疾病, 并且在心脏运动负荷测试中没有缺血迹象。另外招募 30位年龄相匹配的无LVDD的T2DM患者为DM对照组。左心室舒张功能通过心脏组织多普勒评估。心室假性正常化充盈和E’/A’ <1定义为LVDD。结果: 本研究结果显示, 与8周龄糖尿病小鼠和12周龄对照小鼠相比, 12周龄糖尿病小鼠心肌组织中GRK2-mRNA水平及其表达明显增加, 且左心室壁厚度增加和收缩功能增强。胶原蛋白的体积分数(CVF)、胶原蛋白3、P53表达水平和细胞凋亡率在12周龄糖尿病小鼠心肌中也明显升高。人群研究显示, 与DM对照组患者相比, DM+LVDD组患者PBMC中GRK2-mRNA水平明显升高。结论: 在DCM的早期阶段, 心肌组织和PBMC的GRK2水平增加。这些数据支持进一步探讨GRK2在早期DCM诊断中作为临床标志物的可能性。.

journal_name

J Diabetes

journal_title

Journal of diabetes

authors

Lai S,Fu X,Yang S,Zhang S,Lin Q,Zhang M,Chen H

doi

10.1111/1753-0407.12991

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

247-258

issue

eissn

1753-0393

issn

1753-0407

journal_volume

pub_type

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