Hyperglycemic myocardial damage is mediated by proinflammatory cytokine: macrophage migration inhibitory factor.
Hyperglycemic myocardial damage is mediated by proinflammatory cytokine: macrophage migration inhibitory factor.
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高血糖心肌损伤是由促炎细胞因子：巨噬细胞迁移抑制因子介导的
DOI：
10.1371/journal.pone.0016239
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发表时间：
2011-01-25
期刊：
影响因子：
3.7
通讯作者：
Lin SG
中科院分区：
文献类型：
--
作者：
Yu XY;Chen HM;Liang JL;Lin QX;Tan HH;Fu YH;Liu XY;Shan ZX;Li XH;Yang HZ;Yang M;Li Y;Lin SG
背景糖尿病被认为是一种与左心室舒张功能障碍（LVDD）相关的炎症性疾病。本研究旨在检测早期糖尿病心肌病患者心肌组织中巨噬细胞移动抑制因子（MIF）和G蛋白偶联受体激酶2（GRK 2）的表达水平，探讨MIF表达和GRK 2激活的机制。方法收集83例年龄30-64岁的2型糖尿病患者和30例健康男性。心脏多普勒超声心动图评价左室舒张功能。通过ELISA测定血浆MIF水平。为了证实临床观察，我们还研究了糖尿病前期糖耐量受损（IGT）大鼠的MIF表达以及高糖暴露的H9 C2心肌细胞中MIF和GRK 2表达的关系。结果与健康对照组相比，糖尿病患者血浆MIF水平明显升高，糖尿病合并左室舒张功能不全（LVDD）患者血浆MIF水平进一步升高。糖尿病患者血浆MIF水平升高与血糖、糖化血红蛋白和尿白蛋白水平相关。我们观察到大量TUNEL阳性细胞在IGT大鼠的心肌，但在对照组大鼠。此外，我们发现与对照组相比，IGT伴心功能不全的心脏中MIF表达更高。在H9 C2心肌细胞中，MIF和GRK 2的表达以葡萄糖浓度依赖性方式显著增加。此外，GRK 2的表达通过MIF的siRNA敲低和通过H9 C2细胞中CXCR 4的抑制而被消除。结论我们的研究结果表明，高血糖是促炎细胞因子MIF水平升高的一个致病因素，而促炎细胞因子MIF在2型糖尿病患者发生心肌病的过程中发挥着作用。MIF水平升高与糖尿病患者的心功能不全相关，并且MIF的作用由GRK 2介导。
Background Diabetes has been regarded as an inflammatory condition which is associated with left ventricular diastolic dysfunction (LVDD). The purpose of this study was to examine the expression levels of macrophage migration inhibitory factor (MIF) and G protein-coupled receptor kinase 2 (GRK2) in patients with early diabetic cardiomyopathy, and to investigate the mechanisms involved in MIF expression and GRK2 activation. Methods 83 patients in the age range of 30-64 years with type 2 diabetes and 30 matched healthy men were recruited. Left ventricular diastolic function was evaluated by cardiac Doppler echocardiography. Plasma MIF levels were determined by ELISA. To confirm the clinical observation, we also studied MIF expression in prediabetic rats with impaired glucose tolerance (IGT) and relationship between MIF and GRK2 expression in H9C2 cardiomyoblasts exposed to high glucose. Results Compared with healthy subjects, patients with diabetes have significantly increased levels of plasma MIF which was further increased in diabetic patients with Left ventricular diastolic dysfunction (LVDD). The increased plasma MIF levels in diabetic patients correlated with plasma glucose, glycosylated hemoglobin and urine albumin levels. We observed a significant number of TUNEL-positive cells in the myocardium of IGT-rats but not in the control rats. Moreover, we found higher MIF expression in the heart of IGT with cardiac dysfunction compared to that of the controls. In H9C2 cardiomyoblast cells, MIF and GRK2 expression was significantly increased in a glucose concentration-dependant manner. Furthermore, GRK2 expression was abolished by siRNA knockdown of MIF and by the inhibition of CXCR4 in H9C2 cells. Conclusions Our findings indicate that hyperglycemia is a causal factor for increased levels of pro-inflammatory cytokine MIF which plays a role in the development of cardiomyopathy occurring in patients with type 2 diabetes. The elevated levels of MIF are associated with cardiac dysfunction in diabetic patients, and the MIF effects are mediated by GRK2.
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影响因子：
37.8
作者：
Schober, A;Bernhagen, J;Weber, C
通讯作者：
Weber, C
影响因子：
16.2
作者：
Poirier, P;Bogaty, P;Dumesnil, JG
通讯作者：
Dumesnil, JG
影响因子：
10.8
作者：
Takahashi, M;Nishihira, J;Shimada, K
通讯作者：
Shimada, K
影响因子：
5.8
作者：
Dandona, P;Aljada, A;Chaudhuri, A
通讯作者：
Chaudhuri, A
高糖通过巨噬细胞迁移抑制因子和c-Jun N端激酶诱导AC16人心肌细胞凋亡
DOI：
10.1111/j.1440-1681.2010.05420.x
发表时间：
2010-10-01
影响因子：
2.9
作者：
Liang, Jia-Liang;Xiao, Ding-Zhang;Yu, Xi-Yong
通讯作者：
Yu, Xi-Yong