Li Jiang, Liu Lei, Zhang Ruxu, Pan Liqun, Tan Juanying, Ou Mingxin, Luo Xiuju, Peng Jun, Hu Zhongyang
Health Management Medical Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Front Immunol. 2024 Dec 16;15:1488317. doi: 10.3389/fimmu.2024.1488317. eCollection 2024.
Neutrophil extracellular traps (NETs) with inflammatory risk are important contributors to cardiovascular disease, but no definitive information is available in large artery atherosclerotic (LAA) stroke. This study aims to investigate the association between NETs with related inflammatory biomarkers and prognosis of LAA stroke in the Chinese population.
A prospective study involving 145 LAA stroke cases and 121 healthy controls was conducted. Serum levels of MPO-DNA, PAD4, HMGB1, C1q, AIM2, ASC, Caspase-1, IL-1β, IL-6, and IL-8 were determined in all participants. The biomarkers were detected at three time points after stroke onset (24 hours: T1, 48 hours: T2, 7 days: T3) for LAA stroke patients and once for controls. Patients were followed up for 2 years after the ischemic event.
The serum MPO-DNA, PAD4, C1q, IL-1β, IL-6 and IL-8 reach their peak at 24 hours after stroke onset and show a decreasing trend during acute phase. MPO-DNA, AIM2 and IL-1β at baseline were associated with poor outcome at 3 months, further GMDR analysis revealed that the combination of MPO-DNA, AIM2 and IL-1β exert a synergistic effect on the prognosis of LAA stroke (OR: 8.75 95%CI (2.10-32.42)). For time-to-event analysis, MPO-DNA, Caspase-1 and IL-1β at baseline were predictors of MVEs after stroke (HR:4.04 (95%CI 1.28-12.70), 2.33 (95%CI 1.06-5.12) and 4.09 (95%CI 1.39-11.99), respectively).
NETs and related inflammatory biomarkers at baseline predicted outcome at 3 months and late major vascular events following LAA stroke, supporting a rationale of randomized trials for targeted therapy directed at high-risk patients with elevated baseline NETs and related inflammatory biomarkers.
具有炎症风险的中性粒细胞胞外陷阱（NETs）是心血管疾病的重要促成因素，但在大动脉粥样硬化性（LAA）卒中方面尚无确切信息。本研究旨在探讨中国人群中NETs及其相关炎症生物标志物与LAA卒中预后之间的关联。
进行了一项前瞻性研究，纳入145例LAA卒中病例和121例健康对照。测定所有参与者血清中髓过氧化物酶-DNA（MPO-DNA）、瓜氨酸化蛋白水解酶4（PAD4）、高迁移率族蛋白B1（HMGB1）、补体C1q、γ干扰素诱导蛋白16（AIM2）、凋亡相关斑点样蛋白（ASC）、半胱天冬酶-1（Caspase-1）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和白细胞介素-8（IL-8）的水平。LAA卒中患者在卒中发作后的三个时间点（24小时：T1、48小时：T2、7天：T3）检测生物标志物，对照组仅检测一次。缺血事件发生后对患者进行2年随访。
血清MPO-DNA、PAD4、C1q、IL-1β、IL-6和IL-8在卒中发作后24小时达到峰值，并在急性期呈下降趋势。基线时的MPO-DNA、AIM2和IL-1β与3个月时的不良预后相关，进一步的多基因疾病风险预测（GMDR）分析显示，MPO-DNA、AIM2和IL-1β的组合对LAA卒中的预后具有协同作用（比值比：8.75，95%置信区间（2.10 - 32.42））。对于生存分析，基线时的MPO-DNA、Caspase-1和IL-1β是卒中后主要血管事件（MVE）的预测指标（风险比分别为：4.04（95%置信区间1.28 - 12.70）、2.33（95%置信区间1.06 - 5.12）和4.09（95%置信区间1.39 - 11.99））。
基线时的NETs及其相关炎症生物标志物可预测LAA卒中3个月时的预后及晚期主要血管事件，支持针对基线NETs及其相关炎症生物标志物升高的高危患者进行靶向治疗的随机试验的理论依据。
