Elevated levels of pro-thrombotic eNOS-negative platelets in COVID-19 patients

IF 3.7 3区医学 Q1 HEMATOLOGY

Thrombosis research Pub Date : 2024-10-03 DOI:10.1016/j.thromres.2024.109178

Amir Asgari , Aleksandra Franczak , Alex Herchen , Glen C. Jickling , Paul Jurasz

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引用次数: 0

Abstract

Background

Platelet-rich microvascular thrombi are common in severe COVID-19. Endogenous nitric oxide (NO)-signaling limits thrombus formation and previously we identified platelet subpopulations with a differential ability to produce NO based on the presence or absence of endothelial nitric oxide synthase (eNOS). eNOS expression is counter-regulated by cytokines, and COVID-19-associated immune/inflammatory responses may affect the transcriptome profile of megakaryocytes and their platelet progeny.

Objectives

We investigated whether the percentage of eNOS-negative to eNOS-positive platelets increases in COVID-19 patients and whether this change may be due to the actions of pro-inflammatory cytokines on megakaryocytes.

Methods

Platelets were isolated from hospitalized COVID-19 patients and COVID-19-negative controls. Platelet eNOS was measured by flow cytometry and plasma inflammatory cytokines by ELISA. Megakaryocytes from eNOS-GFP transgenic mice and the Meg-01 cell line were characterized to identify an appropriate model to study eNOS-based platelet subpopulation formation in response to inflammatory cytokines.

Results

COVID-19 patients demonstrated a significant increase in eNOS-negative and a concomitant decrease in eNOS-positive platelets compared to controls, and this change was associated with disease severity as assessed by ICU admission. A higher eNOS-negative to –positive platelet percentage was associated with enhanced platelet activation as measured by surface CD62P. Accordingly, COVID-19 patients demonstrated higher TNF-α, IL-6, and IL-1β plasma concentrations than controls. Inflammatory cytokines associated with COVID-19 promoted eNOS-negative Meg-01 formation and enhanced subsequent eNOS-negative platelet-like particle formation.

Conclusions

COVID-19 patients have a higher percentage of eNOS-negative to –positive platelets, likely as a result of inflammatory response reducing megakaryocyte eNOS expression, which predisposes to thrombosis.

查看原文本刊更多论文

COVID-19 患者体内促血栓形成的 eNOS 阴性血小板水平升高。

背景：富含血小板的微血管血栓常见于严重的 COVID-19。内源性一氧化氮（NO）信号限制了血栓的形成，之前我们根据内皮一氧化氮合酶（eNOS）的存在与否确定了具有不同NO生成能力的血小板亚群。eNOS的表达受细胞因子的反调节，COVID-19相关的免疫/炎症反应可能会影响巨核细胞及其血小板后代的转录组特征：我们研究了 COVID-19 患者中 eNOS 阴性血小板与 eNOS 阳性血小板的比例是否增加，以及这种变化是否可能是由于促炎细胞因子对巨核细胞的作用：从住院的 COVID-19 患者和 COVID-19 阴性对照组中分离血小板。用流式细胞术测量血小板 eNOS，用 ELISA 测量血浆中的炎性细胞因子。对来自 eNOS-GFP 转基因小鼠和 Meg-01 细胞系的巨核细胞进行了特征描述，以确定一个合适的模型来研究基于 eNOS 的血小板亚群形成对炎症细胞因子的反应：结果：与对照组相比，COVID-19 患者的 eNOS 阴性血小板显著增加，同时 eNOS 阳性血小板减少，这种变化与入住重症监护室时评估的疾病严重程度有关。根据表面 CD62P 的测量，eNOS 阴性血小板与阳性血小板比例的升高与血小板活化增强有关。因此，COVID-19 患者的 TNF-α、IL-6 和 IL-1β 血浆浓度高于对照组。与 COVID-19 相关的炎症细胞因子促进了 eNOS 阴性 Meg-01 的形成，并增强了随后 eNOS 阴性血小板样颗粒的形成：结论：COVID-19 患者 eNOS 阴性到阳性血小板的比例较高，这可能是炎症反应降低了巨核细胞 eNOS 表达的结果，易导致血栓形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Thrombosis research 医学-外周血管病

CiteScore

14.60

自引率

4.00%

发文量

364

审稿时长

31 days

期刊介绍： Thrombosis Research is an international journal dedicated to the swift dissemination of new information on thrombosis, hemostasis, and vascular biology, aimed at advancing both science and clinical care. The journal publishes peer-reviewed original research, reviews, editorials, opinions, and critiques, covering both basic and clinical studies. Priority is given to research that promises novel approaches in the diagnosis, therapy, prognosis, and prevention of thrombotic and hemorrhagic diseases.