Evidence map›Paper›PMID 41774516›Full record

ArticleBlood2026

Pathogenic role of serpin B3-positive neutrophils in reinforcing thrombus stiffening during ischemic stroke.

Jiankun Zang, Aijun Lu, Bing Yang, Na Tan, Qihuan Liu, Liping Wei, Ying Liang, Sijie Zhou, Zefeng Tan, Xiufeng Xin and 8 more

Abstract read
In one paragraph

Article in Blood, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Jiankun ZangDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.
Aijun LuDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.
Bing YangDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.ORCID 0000-0001-6183-8163
Na TanDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.
Qihuan LiuDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.
Liping WeiDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.
Ying LiangDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.ORCID 0009-0001-4639-0804
Sijie ZhouDepartment of Neurology, The First People's Hospital of Foshan, Foshan, China.
Zefeng TanDepartment of Neurology, The First People's Hospital of Foshan, Foshan, China.
Xiufeng XinDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.
Shengwen HeDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.
Panwen WuDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.
Yufeng LiDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.
Zhifeng XuDepartment of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.ORCID 0000-0002-5929-7772
Xuanlin SuDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.
Hongcheng MaiDepartment of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Anding XuDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.ORCID 0000-0003-3154-0985
Dan LuDepartment of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractThe contribution of immune cells to thrombus architecture and mechanical properties in acute ischemic stroke (AIS) remains poorly understood. Using 3-dimensional imaging and multiplex staining, we mapped immune cells in human stroke thrombi and identified neutrophils as the dominant population. Analysis of 19 thrombi confirmed their positive correlation with collagen, increased stiffness, and poorer clinical outcomes. To preserve spatial context, we developed a laser capture-based proteomic workflow and analyzed thrombus neutrophils from 34 patients with AIS stratified by 90-day outcomes, followed by validation in an independent cohort of 22 patients. Proteomic analysis revealed serpin B3 as a neutrophil-enriched protein strongly correlated with poor prognosis. In murine models of ferric chloride-induced carotid artery thrombosis and middle cerebral artery occlusion, experiments using wild-type, neutrophil-depleted, and Serpinb3a knockout mice demonstrated that neutrophil-derived serpin B3 promotes early thrombus formation, enhances collagen deposition, and contributes to progressive thrombus stiffening. Mechanistically, serpin B3 secreted by neutrophils amplifies thrombus stiffness through upregulation of transforming growth factor β1, neutrophil extracellular traps, and COL1A1. Targeted Serpinb3a knockdown delayed vascular occlusion, improved thrombolysis efficiency, and resulted in better neurological recovery. Collectively, these findings identify a neutrophil-driven mechanism underlying thrombus stiffening and establish SERPINB3 as both a prognostic biomarker and a promising therapeutic target in AIS. This project has been registered with the Chinese Clinical Trial Registration Platform (https://www.chictr.org.cn/index.html) and has successfully passed the review process (registration number: ChiCTR2300077911).

Indexed as

Ischemic StrokeNeutrophilsSerpinsThrombosisAnimalsDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutProteomicsSerpins

Identifiers

PMID41774516
PMCPMC13386090

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.