Collagen-induced p38 MAP kinase activation is a biomarker of platelet hyper-aggregation in patients with diabetes mellitus
Collagen-induced p38 MAP kinase activation is a biomarker of platelet hyper-aggregation in patients with diabetes mellitus
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DOI：
10.1016/j.lfs.2009.07.003
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发表时间：
2009-08-26
期刊：
影响因子：
6.1
通讯作者：
Tokuda, Haruhiko
中科院分区：
文献类型：
--
作者：
Hanai, Yoshiteru;Adachi, Seiji;Tokuda, Haruhiko
目的：我们建立了一种诊断2型糖尿病（DM）患者血小板高聚集的新方法。主要方法：通过测定血小板聚集对胶原的剂量反应，测定个体ED_（50）。根据非糖尿病对照组的正常范围（平均值+/-两个SEM = 0.460 +/- 0.082 μ g/ml，n = 47），将2型糖尿病患者分为高ED 50组（ED 50> 0.542 μ g/ml; n = 32：I组）或低ED 50组（ED 50 < 0.378 μ g/ml; n = 32：II组）。在这些患者中，胶原诱导的磷酸化p38 MAPK和磷酸化p44/p42 MAPK的水平使用蛋白质印迹和酶联免疫吸附测定（ELISA）进行测量。关键发现：在组II中，胶原（0.3和1 μ g/ml）诱导的磷酸化p38 MAPK和磷酸化p44/p42 MAPK的水平通过蛋白质印迹分析测量，发现显著高于组I中的那些。发现个体ED 50与胶原诱导的磷酸化p38 MAPK和磷酸化p44/p42 MAPK水平显著相关。当ELISA用于测量不同DM患者群体（n = 90）中的磷酸化p38 MAPK水平时，也观察到这种相关性。这些结果有力地表明，胶原诱导的p38 MAPK和p44/p42 MAPK的磷酸化水平代表了血小板的高聚集性，并且磷酸化p38 MAPK的定量可以成为血小板高聚集性的新的和有用的诊断生物标志物。糖尿病患者聚集。(C)2009 Elsevier Inc. All rights reserved.
Aims: We developed a novel method for diagnosing platelet hyper-aggregation in patients with type 2 diabetes mellitus (DM).Main methods: By measuring the dose response of platelet aggregation to collagen, an individual ED50 was determined. Based on the normal range identified in non-DM controls (mean +/- two SEM = 0.460 +/- 0.082 mu g/ml, n = 47), type 2 DM patients were divided into high ED50 (ED50 > 0.542 mu g/ml; n = 32: group I) or low ED50 groups (ED50 < 0.378 mu g/ml; n = 32: group II). In these patients, collagen-induced levels of phospho-p38 MAPK and phospho-p44/p42 MAPK were measured using Western blots and enzyme-linked immunosorbent assays (ELISA).Key findings: In group II, the collagen (0.3 and 1 mu g/ml)-induced levels of both phospho-p38 MAPK and phospho-p44/p42 MAPK measured by western blot analysis were found to be significantly higher than those in group I. The individual ED50 was found to be significantly correlated with the collagen-induced levels of phospho-p38 MAPK and phospho-p44/p42 MAPK. This correlation was also observed when ELISA was used to measure phospho-p38 MAPK levels in a different population of DM patients (n = 90).Significance: These results strongly suggest that the phosphorylation levels of collagen-induced p38 MAPK and p44/p42 MAPK represent the hyperaggregability of platelets and that the quantification of phospho-p38 MAPK can be a new and useful diagnostic biomarker of platelet hyper-aggregation in DM patients. (C) 2009 Elsevier Inc. All rights reserved.