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血小板糖蛋白 VI 的表达与短暂性脑缺血发作和中风有关。

Expression of platelet glycoprotein VI is associated with transient ischemic attack and stroke.

机构信息

Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Tübingen, Germany.

出版信息

Eur J Neurol. 2010 Jan;17(1):111-7. doi: 10.1111/j.1468-1331.2009.02754.x. Epub 2009 Jul 21.

Abstract

BACKGROUND AND PURPOSE

Platelet collagen receptor glycoprotein VI (GPVI) contributes significantly to platelet adhesion and thrombus formation. We aimed to investigate GPVI in patients presenting with symptoms of acute cerebrovascular disease and to define GPVI as biomarker for acute stroke.

METHODS

We consecutively evaluated 205 patients, who admitted the stroke unit with symptoms for stroke. Surface expression of the platelet activation markers (GPVI, CD62P, GPIb) was determined by two-color whole blood flow cytometry.

RESULTS

Patients with transient ischemic attack (TIA) (n = 18; 8.8%) as well as with stroke (n = 133; 64.9%) showed a significantly enhanced GPVI expression (mean fluorescence intensity +/- SD) on admission compared to patients with non-ischemic (NI) events (n = 54; 26.3%) (TIA: 20.9 +/- 7.1 vs. NI: 16.2 +/- 3.9; P = 0.002; stroke: 20.4 +/- 5.7 vs. NI; P = 0.002). Neither CD62P nor GPIb surface expression showed a significant difference. Logistic regression analysis revealed that on admission GPVI was associated with stroke independent of conventional laboratory markers such as C-reactive protein, blood glucose, and creatine kinase. Using a receiver operating characteristic curve on GPVI, we have determined the cut off value of 18.2 for stroke. Thus, patients with enhanced GPVI expression levels (>or=18.2) had a 2.4-fold relative risk for stroke. Patients with elevated platelet GPVI expression level had a poorer clinical outcome in cumulative event-free survival for stroke, myocardial infarction, and cerebro-/cardiovascular death at 3-month follow-up (log rank; P = 0.045).

CONCLUSIONS

These findings indicate that platelet GPVI surface expression is significantly enhanced in patients with TIA and stroke compared to patients with NI events. Determination of platelet-specific GPVI may be useful as an early biomarker for cerebral ischemia.

摘要

背景与目的

血小板胶原受体糖蛋白 VI(GPVI)对血小板黏附和血栓形成有重要作用。我们旨在研究急性脑血管病患者的 GPVI,并将其定义为急性脑卒中的生物标志物。

方法

我们连续评估了 205 例因卒中症状入住卒中单元的患者。通过双色全血流式细胞术测定血小板活化标志物(GPVI、CD62P、GPIb)的表面表达。

结果

短暂性脑缺血发作(TIA)患者(n=18;8.8%)和卒中患者(n=133;64.9%)入院时的 GPVI 表达(平均荧光强度±标准差)明显高于非缺血性事件患者(n=54;26.3%)(TIA:20.9±7.1 vs. NI:16.2±3.9;P=0.002;卒中:20.4±5.7 vs. NI;P=0.002)。CD62P 和 GPIb 的表面表达均无显著差异。Logistic 回归分析显示,入院时 GPVI 与卒中相关,独立于 C 反应蛋白、血糖和肌酸激酶等传统实验室标志物。根据 GPVI 的受试者工作特征曲线,我们确定了卒中的截断值为 18.2。因此,表达水平升高的 GPVI(>或=18.2)的患者卒中的相对风险增加了 2.4 倍。在 3 个月随访时,血小板 GPVI 表达水平升高的患者在累积无卒中、心肌梗死和脑/心血管死亡的事件无进展生存中具有较差的临床结局(对数秩检验;P=0.045)。

结论

这些发现表明,与非缺血性事件患者相比,TIA 和卒中患者的血小板 GPVI 表面表达明显增强。血小板特异性 GPVI 的测定可能有助于作为脑缺血的早期生物标志物。

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