Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis.

IF 8 2区 生物学 Q1 BIOLOGY Science China Life Sciences Pub Date : 2024-10-28 DOI:10.1007/s11427-023-2624-9
Xizi Luo, Nan Zhang, Yuntao Liu, Beibei Du, Xuan Wang, Tianxu Zhao, Bingqiang Liu, Shishun Zhao, Jiazhang Qiu, Guoqing Wang
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Abstract

The coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) developed into a global health emergency. Systemic microthrombus caused by SARS-CoV-2 infection is a common complication in patients with COVID-19. Cardiac microthrombosis as a complication of SARS-CoV-2 infection is the primary cause of cardiac injury and death in patietns with severe COVID-19. In this study, we performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors, patients who died during the hypercoagulable period of characteristic coagulation abnormality (CAC), and patients who died during the fibrinolytic period of CAC. We collected 61,187 cells enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. We found that in the course of SARS-CoV-2 infected heart microthrombus, MYO1EhighRASGEF1Bhighmonocyte-derived macrophages promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating chemokines CCL3, CCL5. This series of events is the main cause of cardiac microthrombi following SARS-CoV-2 infection. In a SARS-CoV-2 infected heart microthrombus, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in increased sugar uptake via the glycosaminoglycan synthesis pathway. In addition, high levels of reactive oxygen species generated by elevated iron levels promote increased endogenous malondialdehyde synthesis in a subpopulation of cardiac endothelial cells. This exacerbates endothelial cell dysfunction and exacerbates the coagulopathy process.

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基于单细胞转录组分析解析 SARS-CoV-2 心脏微血栓形成的发育机制
由严重急性呼吸系统综合征冠状病毒-2(SARS-CoV-2)引起的冠状病毒病 2019(COVID-19)疫情已发展成为全球卫生紧急事件。SARS-CoV-2 感染引起的全身微血栓是 COVID-19 患者的常见并发症。作为 SARS-CoV-2 感染并发症的心脏微血栓是严重 COVID-19 患者心脏损伤和死亡的主要原因。在这项研究中,我们对健康供体的右心室游离壁组织、在特征性凝血异常(CAC)的高凝期死亡的患者以及在CAC的纤溶期死亡的患者进行了单细胞测序分析。我们收集了 61,187 个细胞,其中富含 24 个免疫细胞亚群和 13 个心脏驻留细胞亚群。我们发现,在 SARS-CoV-2 感染心脏微血栓的过程中,MYO1EhighRASGEF1Bhighmonocyte-derived macrophages 促进了免疫系统的过度激活,并通过激活趋化因子 CCL3、CCL5 启动了外凝血途径。这一系列事件是 SARS-CoV-2 感染后心脏微血栓形成的主要原因。在 SARS-CoV-2 感染的心脏微血栓中,过度的免疫激活伴随着细胞铁含量的增加,这反过来又促进了氧化应激,加剧了细胞间的竞争。这促使细胞改变其代谢环境,导致通过糖胺聚糖合成途径摄取的糖分增加。此外,铁含量升高产生的大量活性氧会促进心脏内皮细胞亚群的内源性丙二醛合成增加。这加剧了内皮细胞功能障碍,并加剧了凝血过程。
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来源期刊
CiteScore
15.10
自引率
8.80%
发文量
2907
审稿时长
3.2 months
期刊介绍: Science China Life Sciences is a scholarly journal co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China, and it is published by Science China Press. The journal is dedicated to publishing high-quality, original research findings in both basic and applied life science research.
期刊最新文献
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