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血浆蛋白质组学揭示了伴有和不伴有急性缺血性卒中的H型高血压患者的凝血、炎症及代谢变化。

Plasma proteomics reveals coagulation, inflammation, and metabolic shifts in H-type hypertension patients with and without acute ischemic stroke.

作者信息

Zhou Feng, Zhou Lv, Guo Tie, Wang Nianzhen, Hao Haizhen, Zhou Yanhui, Yu Dan

机构信息

Department of Neurology, Affiliated Haikou Hospital at Xiangya Medical School of Central South University, Haikou 570208, Hainan, China.

出版信息

Oncotarget. 2017 Nov 1;8(59):100384-100395. doi: 10.18632/oncotarget.22233. eCollection 2017 Nov 21.

Abstract

Systematic profiling of a larger portion of circulating plasma proteome provide opportunities for unbiased discovery of novel markers to improve diagnostic, therapeutic, or predictive accuracy. This study aimed to identify differentially expressed proteins (DEPs) in plasma that could provide overall insight into the molecular changes of both H- type hypertension (HH) and HH-related acute ischemic stroke (AIS). This study used an iTRAQ-based LC-MS/MS proteomics approach to screen for plasma DEPs in HH patients with and without AIS, and controls. After excluding highly abundant plasma proteins, more than 600 proteins, and their relative levels, were identified. Of these, 26 DEPs, each showing > 1.2-fold change, were identified in HH and HH-related AIS patients compared with controls. Bioinformatics analysis revealed that these DEPs were enriched in 21 functional gene ontology items; "blood coagulation" was the most predominant pathway showing enrichment. Of these, eight DEPs were located in the hub position of networks involved with protein-protein interactions. AT-3, CRP, ApoB, and AHSG were further validated in each group by enzyme-linked immune sorbent assays. Comparing HH-related AIS with HH, the areas under the curve for AT-3, CRP, ApoB, and AHSG were 0.698, 0.892, 0.626, and 0.847, respectively. This proteomic profiling study provided enhanced pathophysiological understanding of the regulatory processes involved in coagulation, inflammation, and metabolism, and identified a panel of novel biomarkers for detecting HH-related AIS during its pre-stroke stage.

摘要

对循环血浆蛋白质组中更大比例进行系统分析,为无偏倚地发现新型标志物以提高诊断、治疗或预测准确性提供了机会。本研究旨在鉴定血浆中差异表达蛋白(DEP),从而全面洞察H型高血压(HH)和HH相关急性缺血性卒中(AIS)的分子变化。本研究采用基于iTRAQ的液相色谱-串联质谱蛋白质组学方法,对有和没有AIS的HH患者以及对照组进行血浆DEP筛选。排除高丰度血浆蛋白后,鉴定出600多种蛋白质及其相对水平。其中,与对照组相比,在HH和HH相关AIS患者中鉴定出26种DEP,每种DEP的变化倍数均>1.2倍。生物信息学分析显示,这些DEP在21个功能基因本体项中富集;“血液凝固”是显示富集的最主要途径。其中,8种DEP位于蛋白质-蛋白质相互作用相关网络的枢纽位置。通过酶联免疫吸附测定对每组中的抗凝血酶-III(AT-3)、C反应蛋白(CRP)、载脂蛋白B(ApoB)和α2-巨球蛋白(AHSG)进行了进一步验证。将HH相关AIS与HH进行比较,AT-3、CRP、ApoB和AHSG的曲线下面积分别为0.698、0.892、0.626和0.847。这项蛋白质组分析研究增强了对凝血、炎症和代谢相关调节过程的病理生理学理解,并鉴定出一组新型生物标志物,用于在HH相关AIS的卒中前期进行检测。

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