关键词: biomarker ischemic stroke liquid chromatography–mass spectrometry (LC-MS) proteomics therapeutic target

来  源:   DOI:10.3390/jcm11020339

Abstract:
(1) Background: The aim of this dynamic-LC/MS-human-serum-proteomic-study was to identify potential proteins-candidates for biomarkers of acute ischemic stroke, their changes during acute phase of stroke and to define potential novel drug-targets. (2) Methods: A total of 32 patients (29-80 years) with acute ischemic stroke were enrolled to the study. The control group constituted 29 demographically-matched volunteers. Subjects with stroke presented clinical symptoms lasting no longer than 24 h, confirmed by neurological-examination and/or new cerebral ischemia visualized in the CT scans (computed tomography). The analysis of plasma proteome was performed using LC-MS (liquid chromatography-mass spectrometry). (3) Results: Ten proteins with significantly different serum concentrations between groups volunteers were: complement-factor-B, apolipoprotein-A-I, fibronectin, alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, heat-shock-cognate-71kDa protein/heat-shock-related-70kDa-protein-2, thymidine phosphorylase-2, cytoplasmic-tryptophan-tRNA-ligase, ficolin-2, beta-Ala-His-dipeptidase. (4) Conclusions: This is the first dynamic LC-MS study performed on a clinical model which differentiates serum proteome of patients in acute phase of ischemic stroke in time series and compares to control group. Listed proteins should be considered as risk factors, markers of ischemic stroke or potential therapeutic targets. Further clinical validation might define their exact role in differential diagnostics, monitoring the course of the ischemic stroke or specifying them as novel drug targets.
摘要:
(1)背景:这项动态LC/MS人血清蛋白质组学研究的目的是鉴定急性缺血性卒中生物标志物的潜在蛋白质候选物,它们在卒中急性期的变化,并定义潜在的新药物靶标。(2)方法:选择32例(29~80岁)急性缺血性脑卒中患者作为研究对象。对照组由29名人口统计学上匹配的志愿者组成。中风患者的临床症状持续时间不超过24小时,通过神经系统检查和/或在CT扫描(计算机断层扫描)中可视化的新脑缺血证实。使用LC-MS(液相色谱-质谱)进行血浆蛋白质组的分析。(3)结果:志愿者组之间血清浓度差异显着的10种蛋白质是:补体因子B,载脂蛋白-A-I,纤连蛋白,α-2-HS-糖蛋白,α-1B-糖蛋白,热休克同源71kDa蛋白/热休克相关70kDa蛋白2,胸苷磷酸化酶2,细胞质色氨酸tRNA连接酶,ficolin-2,β-Ala-His-二肽酶。(4)结论:这是首次在临床模型上进行的动态LC-MS研究,该模型在时间序列上区分了缺血性中风急性期患者的血清蛋白质组,并与对照组进行了比较。列出的蛋白质应被视为危险因素,缺血性卒中的标志物或潜在的治疗靶点。进一步的临床验证可能会定义它们在鉴别诊断中的确切作用,监测缺血性卒中的病程或将其指定为新的药物靶标。
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