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Platelets amplify endotheliopathy in COVID-19.
- Source :
-
Science advances [Sci Adv] 2021 Sep 10; Vol. 7 (37), pp. eabh2434. Date of Electronic Publication: 2021 Sep 08. - Publication Year :
- 2021
-
Abstract
- 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 P2Y <subscript>12</subscript> 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.
Details
- Language :
- English
- ISSN :
- 2375-2548
- Volume :
- 7
- Issue :
- 37
- Database :
- MEDLINE
- Journal :
- Science advances
- Publication Type :
- Academic Journal
- Accession number :
- 34516880
- Full Text :
- https://doi.org/10.1126/sciadv.abh2434