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P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions

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P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions. / Rolling, Christina C; Sowa, Marcin A; Wang, Tricia T; Cornwell, MacIntosh; Myndzar, Khrystyna; Schwartz, Tamar; El Bannoudi, Hanane; Buyon, Jill; Barrett, Tessa J; Berger, Jeffrey S.

in: THROMB HAEMOSTASIS, Jahrgang 123, Nr. 2, 02.2023, S. 231-244.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Rolling, CC, Sowa, MA, Wang, TT, Cornwell, M, Myndzar, K, Schwartz, T, El Bannoudi, H, Buyon, J, Barrett, TJ & Berger, JS 2023, 'P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions', THROMB HAEMOSTASIS, Jg. 123, Nr. 2, S. 231-244. https://doi.org/10.1055/s-0042-1758655

APA

Rolling, C. C., Sowa, M. A., Wang, T. T., Cornwell, M., Myndzar, K., Schwartz, T., El Bannoudi, H., Buyon, J., Barrett, T. J., & Berger, J. S. (2023). P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions. THROMB HAEMOSTASIS, 123(2), 231-244. https://doi.org/10.1055/s-0042-1758655

Vancouver

Rolling CC, Sowa MA, Wang TT, Cornwell M, Myndzar K, Schwartz T et al. P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions. THROMB HAEMOSTASIS. 2023 Feb;123(2):231-244. https://doi.org/10.1055/s-0042-1758655

Bibtex

@article{eb8da29129664b5f9649ec3cda8b9160,
title = "P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions",
abstract = "BACKGROUND:  Monocyte-platelet aggregates (MPAs) represent the crossroads between thrombosis and inflammation, and targeting this axis may suppress thromboinflammation. While antiplatelet therapy (APT) reduces platelet-platelet aggregation and thrombosis, its effects on MPA and platelet effector properties on monocytes are uncertain.OBJECTIVES:  To analyze the effect of platelets on monocyte activation and APT on MPA and platelet-induced monocyte activation.METHODS:  Agonist-stimulated whole blood was incubated in the presence of P-selectin, PSGL1, PAR1, P2Y12, GP IIb/IIIa, and COX-1 inhibitors and assessed for platelet and monocyte activity via flow cytometry. RNA-Seq of monocytes incubated with platelets was used to identify platelet-induced monocyte transcripts and was validated by RT-qPCR in monocyte-PR co-incubation ± APT.RESULTS:  Consistent with a proinflammatory platelet effector role, MPAs were increased in patients with COVID-19. RNA-Seq revealed a thromboinflammatory monocyte transcriptome upon incubation with platelets. Monocytes aggregated to platelets expressed higher CD40 and tissue factor than monocytes without platelets (p < 0.05 for each). Inhibition with P-selectin (85% reduction) and PSGL1 (87% reduction) led to a robust decrease in MPA. P2Y12 and PAR1 inhibition lowered MPA formation (30 and 21% reduction, p < 0.05, respectively) and decreased monocyte CD40 and TF expression, while GP IIb/IIIa and COX1 inhibition had no effect. Pretreatment of platelets with P2Y12 inhibitors reduced the expression of platelet-mediated monocyte transcription of proinflammatory SOCS3 and OSM. CONCLUSIONS:  Platelets skew monocytes toward a proinflammatory phenotype. Among traditional APTs, P2Y12 inhibition attenuates platelet-induced monocyte activation.",
author = "Rolling, {Christina C} and Sowa, {Marcin A} and Wang, {Tricia T} and MacIntosh Cornwell and Khrystyna Myndzar and Tamar Schwartz and {El Bannoudi}, Hanane and Jill Buyon and Barrett, {Tessa J} and Berger, {Jeffrey S}",
note = "Thieme. All rights reserved.",
year = "2023",
month = feb,
doi = "10.1055/s-0042-1758655",
language = "English",
volume = "123",
pages = "231--244",
journal = "THROMB HAEMOSTASIS",
issn = "0340-6245",
publisher = "Schattauer",
number = "2",

}

RIS

TY - JOUR

T1 - P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions

AU - Rolling, Christina C

AU - Sowa, Marcin A

AU - Wang, Tricia T

AU - Cornwell, MacIntosh

AU - Myndzar, Khrystyna

AU - Schwartz, Tamar

AU - El Bannoudi, Hanane

AU - Buyon, Jill

AU - Barrett, Tessa J

AU - Berger, Jeffrey S

N1 - Thieme. All rights reserved.

PY - 2023/2

Y1 - 2023/2

N2 - BACKGROUND:  Monocyte-platelet aggregates (MPAs) represent the crossroads between thrombosis and inflammation, and targeting this axis may suppress thromboinflammation. While antiplatelet therapy (APT) reduces platelet-platelet aggregation and thrombosis, its effects on MPA and platelet effector properties on monocytes are uncertain.OBJECTIVES:  To analyze the effect of platelets on monocyte activation and APT on MPA and platelet-induced monocyte activation.METHODS:  Agonist-stimulated whole blood was incubated in the presence of P-selectin, PSGL1, PAR1, P2Y12, GP IIb/IIIa, and COX-1 inhibitors and assessed for platelet and monocyte activity via flow cytometry. RNA-Seq of monocytes incubated with platelets was used to identify platelet-induced monocyte transcripts and was validated by RT-qPCR in monocyte-PR co-incubation ± APT.RESULTS:  Consistent with a proinflammatory platelet effector role, MPAs were increased in patients with COVID-19. RNA-Seq revealed a thromboinflammatory monocyte transcriptome upon incubation with platelets. Monocytes aggregated to platelets expressed higher CD40 and tissue factor than monocytes without platelets (p < 0.05 for each). Inhibition with P-selectin (85% reduction) and PSGL1 (87% reduction) led to a robust decrease in MPA. P2Y12 and PAR1 inhibition lowered MPA formation (30 and 21% reduction, p < 0.05, respectively) and decreased monocyte CD40 and TF expression, while GP IIb/IIIa and COX1 inhibition had no effect. Pretreatment of platelets with P2Y12 inhibitors reduced the expression of platelet-mediated monocyte transcription of proinflammatory SOCS3 and OSM. CONCLUSIONS:  Platelets skew monocytes toward a proinflammatory phenotype. Among traditional APTs, P2Y12 inhibition attenuates platelet-induced monocyte activation.

AB - BACKGROUND:  Monocyte-platelet aggregates (MPAs) represent the crossroads between thrombosis and inflammation, and targeting this axis may suppress thromboinflammation. While antiplatelet therapy (APT) reduces platelet-platelet aggregation and thrombosis, its effects on MPA and platelet effector properties on monocytes are uncertain.OBJECTIVES:  To analyze the effect of platelets on monocyte activation and APT on MPA and platelet-induced monocyte activation.METHODS:  Agonist-stimulated whole blood was incubated in the presence of P-selectin, PSGL1, PAR1, P2Y12, GP IIb/IIIa, and COX-1 inhibitors and assessed for platelet and monocyte activity via flow cytometry. RNA-Seq of monocytes incubated with platelets was used to identify platelet-induced monocyte transcripts and was validated by RT-qPCR in monocyte-PR co-incubation ± APT.RESULTS:  Consistent with a proinflammatory platelet effector role, MPAs were increased in patients with COVID-19. RNA-Seq revealed a thromboinflammatory monocyte transcriptome upon incubation with platelets. Monocytes aggregated to platelets expressed higher CD40 and tissue factor than monocytes without platelets (p < 0.05 for each). Inhibition with P-selectin (85% reduction) and PSGL1 (87% reduction) led to a robust decrease in MPA. P2Y12 and PAR1 inhibition lowered MPA formation (30 and 21% reduction, p < 0.05, respectively) and decreased monocyte CD40 and TF expression, while GP IIb/IIIa and COX1 inhibition had no effect. Pretreatment of platelets with P2Y12 inhibitors reduced the expression of platelet-mediated monocyte transcription of proinflammatory SOCS3 and OSM. CONCLUSIONS:  Platelets skew monocytes toward a proinflammatory phenotype. Among traditional APTs, P2Y12 inhibition attenuates platelet-induced monocyte activation.

U2 - 10.1055/s-0042-1758655

DO - 10.1055/s-0042-1758655

M3 - SCORING: Journal article

C2 - 36630990

VL - 123

SP - 231

EP - 244

JO - THROMB HAEMOSTASIS

JF - THROMB HAEMOSTASIS

SN - 0340-6245

IS - 2

ER -