纵向研究揭示了缺血性脑卒中后各亚型的长期促炎蛋白组学特征。

Longitudinal Study Reveals Long-Term Proinflammatory Proteomic Signature After Ischemic Stroke Across Subtypes.

机构信息

Institute of Biomedicine, Department of Laboratory Medicine, the Sahlgrenska Academy, University of Gothenburg, Sweden (T.M.S., A.A., C.B., C.J.).

Bioinformatics Core Facility, University of Gothenburg, Sweden (B.A.).

出版信息

Stroke. 2022 Sep;53(9):2847-2858. doi: 10.1161/STROKEAHA.121.038349. Epub 2022 Jun 10.

DOI:10.1161/STROKEAHA.121.038349

PMID:35686557

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9389938/

Abstract

BACKGROUND

Inflammation contributes both to the pathogenesis of stroke and the response to brain injury. We aimed to identify proteins reflecting the acute-phase response and proteins more likely to reflect proinflammatory processes present before stroke by broadly profiling inflammation-related plasma proteins in a longitudinal ischemic stroke study.

METHODS

Participants were from a Swedish ischemic stroke cohort (SAHLSIS [Sahlgrenska Academy Study on Ischemic Stroke], n=600 cases and n=600 controls). Plasma levels of 65 proteins including chemokines, interleukins, surface molecules, and immune receptors were measured once in controls and at 3× in cases: during the acute phase, after 3 months, and for a subgroup (n=223) at 7-year follow-up. Associations between proteins and ischemic stroke or subtype were investigated in multivariable binary regression models corrected for age, sex, vascular risk factors, and multiple testing.

RESULTS

In the acute phase, 48 proteins were significantly and independently associated with ischemic stroke (false discovery rate adjusted <0.05). At 3-month follow-up, 51 proteins and at 7-year follow-up 50 proteins were associated with ischemic stroke. The majority of proteins were upregulated in cases compared with controls (n=34 at all time points) and the most upregulated were CXCL5 (CXC chemokine ligand 5) and OSM (oncostatin M). Generally, large artery and cardioembolic stroke had the highest protein levels. However, several interesting subtype-specific differences were also detected at each time point.

CONCLUSIONS

We found inflammation-related proteins that were differentially regulated in ischemic stroke cases compared with controls only in the acute phase and others that remained elevated also at later time points. This latter group of proteins could reflect underlying pathophysiological processes of relevance. Future studies both in terms of disease risk and prognostication are warranted.

摘要

背景

炎症既参与中风的发病机制，也参与脑损伤的反应。我们旨在通过在一项纵向缺血性中风研究中广泛分析与炎症相关的血浆蛋白，来鉴定反映急性期反应的蛋白和更有可能反映中风前促炎过程的蛋白。

方法

参与者来自瑞典缺血性中风队列（SAHLSIS[萨赫勒学院缺血性中风研究]，病例 600 例，对照组 600 例）。在对照组中检测了 65 种蛋白（包括趋化因子、白细胞介素、表面分子和免疫受体）的血浆水平，在病例中检测了 3 次：急性期、3 个月后和亚组（n=223）7 年随访时。使用多变量二元回归模型，在校正年龄、性别、血管危险因素和多重检验后，研究了蛋白与缺血性中风或亚型之间的关联。

结果

在急性期，48 种蛋白与缺血性中风显著且独立相关（假发现率调整后<0.05）。在 3 个月随访时，51 种蛋白和 7 年随访时 50 种蛋白与缺血性中风相关。与对照组相比，大多数蛋白在病例中上调（所有时间点 n=34），上调最明显的是 CXCL5（CXC 趋化因子配体 5）和 OSM（oncostatin M）。一般来说，大动脉和心源性栓塞性中风的蛋白水平最高。然而，在每个时间点也检测到了一些有趣的亚型特异性差异。