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重症新冠肺炎患者中靶向凝血和纤维蛋白溶解的循环微小RNA

Circulating microRNAs targeting coagulation and fibrinolysis in patients with severe COVID-19.

作者信息

Helin Tuukka A, Lemponen Marja, Immonen Katariina, Lakkisto Päivi, Joutsi-Korhonen Lotta

机构信息

HUS Diagnostic Center, Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, POB 720, Helsinki, 00029, Finland.

Minerva Foundation Institute for Medical Research, Helsinki, Finland.

出版信息

Thromb J. 2024 Sep 5;22(1):80. doi: 10.1186/s12959-024-00649-w.

Abstract

BACKGROUND

Coronavirus-19 disease (COVID-19) frequently causes coagulation disturbances. Data remains limited on the effects of microRNAs (miRNAs) on coagulation during COVID-19 infection. We aimed to analyze the comprehensive miRNA profile as well as coagulation markers and blood count in hospitalized COVID-19 patients.

METHODS

Citrated plasma samples from 40 patients (24 men and 16 women) hospitalized for COVID-19 were analyzed. Basic coagulation tests, von Willebrand factor (VWF), ADAMTS13, blood count, C-reactive protein, and 27 miRNAs known to associate with thrombosis or platelet activation were analyzed. MiRNAs were analyzed using quantitative reverse transcription polymerase chain reaction (RT qPCR), with 10 healthy controls serving as a comparator.

RESULTS

Among the patients, 15/36 (41%) had platelet count of over 360 × 10/L and 10/36 (28%) had low hemoglobin of < 100 g/L, while 26/37 (72%) had high VWF of over 200 IU/dL. Patients had higher levels of the miRNAs miR-27b-3p, miR-320a-3p, miR-320b-3p, and miR-424-5p, whereas levels of miR-103a-3p and miR-145-5p were lower than those in healthy controls. In total, 11 miRNAs were associated with platelet count. Let-7b-3p was associated with low hemoglobin levels of < 100 g/L. miR-24-3p, miR-27b-3p, miR-126-3p, miR-145-5p and miR-338-5p associated with high VWF.

CONCLUSION

COVID-19 patients differentially express miRNAs with target genes involved in fibrinolysis inhibition, coagulation activity, and increased inflammatory response. These findings support the notion that COVID-19 widely affects hemostasis, including platelets, coagulation and fibrinolysis.

摘要

背景

新型冠状病毒肺炎(COVID-19)常导致凝血功能紊乱。关于微小RNA(miRNA)在COVID-19感染期间对凝血的影响的数据仍然有限。我们旨在分析住院COVID-19患者的综合miRNA谱以及凝血标志物和血细胞计数。

方法

分析了40例因COVID-19住院患者(24例男性和16例女性)的枸橼酸盐血浆样本。分析了基本凝血试验、血管性血友病因子(VWF)、含血小板解聚蛋白金属蛋白酶13(ADAMTS13)、血细胞计数、C反应蛋白以及27种已知与血栓形成或血小板活化相关的miRNA。使用定量逆转录聚合酶链反应(RT qPCR)分析miRNA,以10名健康对照作为比较对象。

结果

在患者中,15/36(41%)的血小板计数超过360×10⁹/L,10/36(28%)的血红蛋白水平低至<100 g/L,而26/37(72%)的VWF水平高至超过200 IU/dL。患者的miR-27b-3p、miR-320a-3p、miR-320b-3p和miR-424-5p水平较高,而miR-103a-3p和miR-145-5p水平低于健康对照。总共11种miRNA与血小板计数相关。Let-7b-3p与<100 g/L的低血红蛋白水平相关。miR-24-3p、miR-27b-3p、miR-126-3p、miR-145-5p和miR-338-5p与高VWF相关。

结论

COVID-19患者差异表达的miRNA具有参与纤溶抑制、凝血活性和炎症反应增加的靶基因。这些发现支持了COVID-19广泛影响止血,包括血小板、凝血和纤溶的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea1f/11375984/196cb8ac69a0/12959_2024_649_Fig1_HTML.jpg

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