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肽基精氨酸脱亚氨酶 4 作为颈动脉狭窄斑块不稳定的可能生物标志物。

Peptidylarginine Deiminase 4 as a Possible Biomarker of Plaque Instability in Carotid Artery Stenosis.

机构信息

Department of Neurosurgery and Interventional Neuroradiology, Hiroshima City Asa Citizens Hospital, 2-1-1 Kabeminami, Asakitaku, 731 0293 Hiroshima, Japan.

Department of Neurosurgery and Interventional Neuroradiology, Hiroshima City Asa Citizens Hospital, 2-1-1 Kabeminami, Asakitaku, 731 0293 Hiroshima, Japan; Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

出版信息

J Stroke Cerebrovasc Dis. 2021 Jul;30(7):105816. doi: 10.1016/j.jstrokecerebrovasdis.2021.105816. Epub 2021 Apr 24.

DOI:10.1016/j.jstrokecerebrovasdis.2021.105816
PMID:33906071
Abstract

BACKGROUND AND PURPOSE

Neutrophil extracellular traps (NETs) exhibit pro-inflammatory and pro-thrombotic properties. However, they have only been reported as important regulators in atherosclerosis, especially in atherothrombosis. We investigated the presence of NETs and plaque instability in patients with carotid artery stenosis.

MATERIAL AND METHODS

A total of 39 consecutive patients with carotid artery stenosis were evaluated. All patients underwent carotid artery stenting (CAS) with dual protection (simultaneous flow reversal + distal filter) and blood aspiration as a method of distal embolism prevention. Local arterial blood was aspirated at the stent site and peptidylarginine deiminase 4 (PAD4), which is essential for the formation of NETs, was measured. The relationships between PAD4 and the patient profile, blood examination and plaque data were investigated.

RESULTS

The mean value of PAD4 in local arterial blood in CAS was 0.5 ng/ml. Bivariate analysis demonstrated that PAD4 was associated with the neutrophil to lymphocyte ratio (p = 0.007), high-density lipoprotein (p = 0.02), triglycerides to high-density lipoprotein ratio (p = 0.007), ulceration (p = 0.02) and plaque contrast enhancement on T1 black blood imaging (p = 0.03). In multiple linear regression analyses, PAD4 was correlated with the neutrophil to lymphocyte ratio (p = 0.01) and ulceration (p = 0.01, cut-off value: 0.49 odds ratio: 19.3).

CONCLUSIONS

PAD4, representative of the presence of NETs, was high in carotid plaques with unstable features. The neutrophil to lymphocyte ratio in peripheral blood was suggested to be a biomarker of vulnerable plaques. Elucidating the role of NETs may aid in clarifying factors that promote the instability of carotid plaques.

摘要

背景与目的

中性粒细胞胞外诱捕网(NETs)具有促炎和促血栓形成的特性。然而,它们仅被报道为动脉粥样硬化,特别是动脉粥样硬化血栓形成的重要调节因子。我们研究了颈动脉狭窄患者中 NETs 和斑块不稳定的存在情况。

材料和方法

共评估了 39 例连续的颈动脉狭窄患者。所有患者均接受颈动脉支架置入术(CAS),采用双重保护(同时血流反转+远端滤网)和血液抽吸作为预防远端栓塞的方法。在支架部位抽吸局部动脉血,测量参与 NETs 形成的肽基精氨酸脱亚氨酶 4(PAD4)的含量。研究 PAD4 与患者特征、血液检查和斑块数据之间的关系。

结果

CAS 局部动脉血中 PAD4 的平均值为 0.5ng/ml。双变量分析表明,PAD4 与中性粒细胞与淋巴细胞比值(p=0.007)、高密度脂蛋白(p=0.02)、甘油三酯与高密度脂蛋白比值(p=0.007)、溃疡(p=0.02)和 T1 黑血成像上的斑块对比增强(p=0.03)有关。在多元线性回归分析中,PAD4 与中性粒细胞与淋巴细胞比值(p=0.01)和溃疡(p=0.01,截断值:0.49,比值比:19.3)相关。

结论

代表 NETs 存在的 PAD4 在具有不稳定特征的颈动脉斑块中较高。外周血中的中性粒细胞与淋巴细胞比值提示是易损斑块的生物标志物。阐明 NETs 的作用可能有助于阐明促进颈动脉斑块不稳定的因素。

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