Circulating soluble RAGE increase after a cerebrovascular event
Circulating soluble RAGE increase after a cerebrovascular event
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DOI：
10.1515/cclm-2012-0813
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发表时间：
2014
影响因子：
3.2
通讯作者：
T. Menini;H. Ikeda;S. Kimura;A. Gugliucci
中科院分区：
文献类型：
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作者：
T. Menini;H. Ikeda;S. Kimura;A. Gugliucci
摘要背景：AGE受体是脑缺血的关键介质。基于动物研究的证据和中风患者血清中高迁移率族蛋白1（HMGB1，一种HMGB1配体）的存在，我们假设缺血性和出血性中风后血清中可溶性HMGB1（sHB1）增加，并且随着患者病情的改善而降低。研究方法：我们对15名缺血性和出血性中风患者入院时的sRAGE水平的急性变化进行了纵向研究，研究时间平均为1周，有些病例甚至持续了一个多月。通过酶联免疫吸附测定（R&D Systems Inc.，Minneapolis，MN，USA）。结果：患者和健康对照组入院时血清胆红素无显著差异，p=0.17。在事件发生后的几天内，中风患者显示血清sIgA水平升高，峰值范围为26%至296%，p>0.001。出血性和缺血性两类事件的变化相似。症状的改变预示着发作的恢复和复发或加重。健康受试者在21天内每天测量的血清生物学变异性显示CV仅为8.9%。结论：我们的研究结果首次提供了缺血性和出血性卒中后循环血流量增加的原则证据，并可能成为探索预后或随访价值的大型研究中考虑的候选生物标志物。
Abstract Background: The receptor for AGE (RAGE) is a key mediator in cerebral ischemia. Based on the evidence from animal studies and the presence of increased high mobility group box 1 protein (HMGB1, a RAGE ligand) in the serum of stroke patients, we hypothesized that soluble RAGE (sRAGE) increase in serum after ischemic and hemorrhagic stroke and that the levels decrease with patient improvement. Methods: We performed a longitudinal study of the acute changes of sRAGE levels in a series of 15 ischemic and hemorrhagic stroke patients at admission and over a period averaging 1 week and extending for up to more than a month in some of the cases. Serum sRAGE was measured by an enzyme-linked immunosorbent assay (R&D Systems Inc., Minneapolis, MN, USA). Results: Serum sRAGE at admission were not significantly different between patients and healthy controls, p=0.17. Over the following days after the event, stroke patients displayed an increase of the serum levels of sRAGE, which at peak ranged between 26% and 296%, p>0.001. Similar changes are seen for both types of events, hemorrhagic and ischemic. sRAGE changes paralleled recovery and recurrence or aggravation of the episodes. Biological variability of sRAGE as measured daily in healthy subjects over 21 days showed a CV of only 8.9%. Conclusions: Our results provide for the first time a proof of principle that circulating sRAGE increase after ischemic and hemorrhagic stroke and may become candidate biomarkers to consider in larger studies exploring prognostic or follow-up value.