Assessment of associations between neutrophil extracellular trap biomarkers in blood and thrombi in acute ischemic stroke patients.

IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Journal of Thrombosis and Thrombolysis Pub Date : 2024-08-01 Epub Date: 2024-06-09 DOI:10.1007/s11239-024-03004-y
Tristan Baumann, Nicole de Buhr, Nicole Blume, Maria M Gabriel, Johanna Ernst, Leonie Fingerhut, Rabea Imker, Omar Abu-Fares, Mark Kühnel, Danny D Jonigk, Friedrich Götz, Christine Falk, Karin Weissenborn, Gerrit M Grosse, Ramona Schuppner
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Abstract

Inflammation including immunothrombosis by neutrophil extracellular traps (NETs) has important implications in acute ischemic stroke and can affect reperfusion status, susceptibility to stroke associated infections (SAI) as well as functional clinical outcome. NETs were shown to be prevalent in stroke thrombi and NET associated markers were found in stroke patients' blood. However, little is known whether blood derived NET markers reflect the amount of NETs in thrombi. Conclusions from blood derived markers to thrombus composition might open avenues for novel strategies in diagnostic and therapeutic approaches. We prospectively recruited 166 patients with acute ischemic stroke undergoing mechanical thrombectomy between March 2018 and May 2021. Available thrombi (n = 106) were stained for NET markers DNA-histone-1 complexes and myeloperoxidase (MPO). Cell free DNA (cfDNA), deoxyribonuclease (DNase) activity, MPO-histone complexes and a cytokine-panel were measured before thrombectomy and after seven days. Clinical data, including stroke etiology, reperfusion status, SAI and functional outcome after rehabilitation, were collected of all patients. NET markers were present in all thrombi. At onset the median concentration of cfDNA in blood was 0.19 µg/ml increasing to 0.30 µg/ml at 7 days. Median DNase activity at onset was 4.33 pmol/min/ml increasing to 4.96 pmol/min/ml at 7 days. Within thrombi DNA-histone-1 complexes and MPO correlated with each other (ρ = 0.792; p < 0.001). Moreover, our study provides evidence for an association between the amount of NETs and endogenous DNase activity in blood with amounts of NETs in cerebral thrombi. However, these associations need to be confirmed in larger cohorts, to investigate the potential clinical implications for individualized therapeutic and diagnostic approaches in acute ischemic stroke.

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评估急性缺血性脑卒中患者血液中中性粒细胞胞外捕获物生物标记物与血栓之间的关联。
中性粒细胞胞外捕获物(NETs)引起的炎症(包括免疫血栓)对急性缺血性中风有重要影响,可影响再灌注状态、中风相关感染(SAI)的易感性以及临床功能预后。研究表明,中风血栓中普遍存在 NET,中风患者的血液中也发现了与 NET 相关的标记物。然而,对于血液中的 NET 标记物是否能反映血栓中 NET 的数量却知之甚少。从血液衍生标记物到血栓组成的结论可能为诊断和治疗方法的新策略开辟了道路。我们在 2018 年 3 月至 2021 年 5 月期间前瞻性地招募了 166 名接受机械血栓切除术的急性缺血性脑卒中患者。对可用血栓(n = 106)进行了NET标记物DNA-组蛋白-1复合物和髓过氧化物酶(MPO)染色。在血栓切除术前和七天后测量细胞游离 DNA(cfDNA)、脱氧核糖核酸酶(DNase)活性、MPO-组蛋白复合物和细胞因子面板。收集了所有患者的临床数据,包括中风病因、再灌注状态、SAI 和康复后的功能结果。所有血栓中都含有 NET 标记物。发病时,血液中 cfDNA 的中位浓度为 0.19 微克/毫升,7 天后增至 0.30 微克/毫升。发病时 DNase 活性的中位数为 4.33 pmol/min/ml,7 天后增至 4.96 pmol/min/ml。血栓内的 DNA 组蛋白-1 复合物和 MPO 相互关联(ρ = 0.792; p
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来源期刊
CiteScore
9.20
自引率
0.00%
发文量
112
审稿时长
4-8 weeks
期刊介绍: The Journal of Thrombosis and Thrombolysis is a long-awaited resource for contemporary cardiologists, hematologists, vascular medicine specialists and clinician-scientists actively involved in treatment decisions and clinical investigation of thrombotic disorders involving the cardiovascular and cerebrovascular systems. The principal focus of the Journal centers on the pathobiology of thrombosis and vascular disorders and the use of anticoagulants, platelet antagonists, cell-based therapies and interventions in scientific investigation, clinical-translational research and patient care. The Journal will publish original work which emphasizes the interface between fundamental scientific principles and clinical investigation, stimulating an interdisciplinary and scholarly dialogue in thrombosis and vascular science. Published works will also define platforms for translational research, drug development, clinical trials and patient-directed applications. The Journal of Thrombosis and Thrombolysis'' integrated format will expand the reader''s knowledge base and provide important insights for both the investigation and direct clinical application of the most rapidly growing fields in medicine-thrombosis and vascular science.
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