Platelets amplify endotheliopathy in COVID-19
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Platelets amplify endotheliopathy in COVID-19. / Barrett, Tessa J; Cornwell, MacIntosh; Myndzar, Khrystyna; Rolling, Christina C; Xia, Yuhe; Drenkova, Kamelia; Biebuyck, Antoine; Fields, Alexander T; Tawil, Michael; Luttrell-Williams, Elliot; Yuriditsky, Eugene; Smith, Grace; Cotzia, Paolo; Neal, Matthew D; Kornblith, Lucy Z; Pittaluga, Stefania; Rapkiewicz, Amy V; Burgess, Hannah M; Mohr, Ian; Stapleford, Kenneth A; Voora, Deepak; Ruggles, Kelly; Hochman, Judith; Berger, Jeffrey S.
in: SCI ADV, Jahrgang 7, Nr. 37, 10.09.2021, S. eabh2434.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Platelets amplify endotheliopathy in COVID-19
AU - Barrett, Tessa J
AU - Cornwell, MacIntosh
AU - Myndzar, Khrystyna
AU - Rolling, Christina C
AU - Xia, Yuhe
AU - Drenkova, Kamelia
AU - Biebuyck, Antoine
AU - Fields, Alexander T
AU - Tawil, Michael
AU - Luttrell-Williams, Elliot
AU - Yuriditsky, Eugene
AU - Smith, Grace
AU - Cotzia, Paolo
AU - Neal, Matthew D
AU - Kornblith, Lucy Z
AU - Pittaluga, Stefania
AU - Rapkiewicz, Amy V
AU - Burgess, Hannah M
AU - Mohr, Ian
AU - Stapleford, Kenneth A
AU - Voora, Deepak
AU - Ruggles, Kelly
AU - Hochman, Judith
AU - Berger, Jeffrey S
PY - 2021/9/10
Y1 - 2021/9/10
N2 - 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.
AB - 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.
U2 - 10.1126/sciadv.abh2434
DO - 10.1126/sciadv.abh2434
M3 - SCORING: Journal article
C2 - 34516880
VL - 7
SP - eabh2434
JO - SCI ADV
JF - SCI ADV
SN - 2375-2548
IS - 37
ER -