Platelets amplify endotheliopathy in COVID-19.
Platelets amplify endotheliopathy in COVID-19.
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DOI：
10.1126/sciadv.abh2434
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发表时间：
2021-09-10
期刊：
影响因子：
13.6
通讯作者：
Berger JS
中科院分区：
文献类型：
--
作者：
Barrett TJ;Cornwell M;Myndzar K;Rolling CC;Xia Y;Drenkova K;Biebuyck A;Fields AT;Tawil M;Luttrell-Williams E;Yuriditsky E;Smith G;Cotzia P;Neal MD;Kornblith LZ;Pittaluga S;Rapkiewicz AV;Burgess HM;Mohr I;Stapleford KA;Voora D;Ruggles K;Hochman J;Berger JS
血小板源性MRP 8/14放大COVID-19中的内皮病变鉴于COVID-19中血小板过度活跃表型的证据，我们研究了COVID-19血小板对内皮细胞（EC）的效应细胞特性。EC和血小板RNA测序的整合显示，COVID-19中的血小板释放因子促进了炎性高凝性内皮病。我们鉴定出S100 A8和S100 A9是在COVID-19血小板中富集的转录物，并由SARS-CoV-2感染的巨核细胞诱导。与增加的基因表达一致，S100 A8/A9的异二聚体蛋白产物，骨髓相关蛋白（MRP）8/14，相对于对照，从COVID-19患者的血小板中释放的程度更大。我们证明，血小板衍生的MRP 8/14激活EC，促进炎症性高凝表型，是COVID-19患者临床结局不佳的重要因素。最后，我们提出的证据表明，靶向血小板P2 Y12代表了一个有前途的候选人，以减少促炎血小板内皮细胞相互作用。总之，这些发现证明了血小板及其活化诱导的内皮病在COVID-19中的作用以前未被重视。
Platelet-derived MRP8/14 amplifies endotheliopathy in COVID-19. Given the evidence for a hyperactive platelet phenotype in COVID-19, we investigated effector cell properties of COVID-19 platelets on endothelial cells (ECs). Integration of EC and platelet RNA sequencing revealed that platelet-released factors in COVID-19 promote an inflammatory hypercoagulable endotheliopathy. We identified S100A8 and S100A9 as transcripts enriched in COVID-19 platelets and were induced by megakaryocyte infection with SARS-CoV-2. Consistent with increased gene expression, the heterodimer protein product of S100A8/A9, myeloid-related protein (MRP) 8/14, was released to a greater extent by platelets from COVID-19 patients relative to controls. We demonstrate that platelet-derived MRP8/14 activates ECs, promotes an inflammatory hypercoagulable phenotype, and is a significant contributor to poor clinical outcomes in COVID-19 patients. Last, we present evidence that targeting platelet P2Y12 represents a promising candidate to reduce proinflammatory platelet-endothelial interactions. Together, these findings demonstrate a previously unappreciated role for platelets and their activation-induced endotheliopathy in COVID-19.
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