open access

Vol 26, No 6 (2019)
Original articles — Basic science and experimental cardiology
Published online: 2018-04-17
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P2Y12 antagonist ticagrelor inhibits the release of procoagulant extracellular vesicles from activated platelets

Aleksandra Gasecka, Rienk Nieuwland, Edwin van der Pol, Najat Hajji, Agata Ćwiek, Kinga Pluta, Michał Konwerski, Krzysztof J. Filipiak
DOI: 10.5603/CJ.a2018.0045
·
Pubmed: 29671861
·
Cardiol J 2019;26(6):782-789.

open access

Vol 26, No 6 (2019)
Original articles — Basic science and experimental cardiology
Published online: 2018-04-17

Abstract

Background: Activated platelets release platelet extracellular vesicles (PEVs). Adenosine diphosphate
(ADP) receptors P2Y1 and P2Y12 both play a role in platelet activation, The present hypothesis herein
is that the inhibition of these receptors may affect the release of PEVs.
Methods: Platelet-rich plasma from 10 healthy subjects was incubated with saline, P2Y1 antagonist
MRS2179 (100 μM), P2Y12 antagonist ticagrelor (1 μM), and a combination of both antagonists.
Platelets were activated by ADP (10 μM) under stirring conditions at 37°C. Platelet reactivity was
assessed by impedance aggregometry. Concentrations of PEVs– (positive for CD61 but negative for
P-selectin and phosphatidylserine) and PEVs+ (positive for all) were determined by a state-of-the-art
flow cytometer. Procoagulant activity of PEVs was measured by a fibrin generation test.
Results: ADP-induced aggregation (57 ± 13 area under curve {AUC] units) was inhibited 73%
by the P2Y1 antagonist, 86% by the P2Y12 antagonist, and 95% when combined (p < 0.001 for all).
The release of PEVs– (2.9 E ± 0.8 × 108/mL) was inhibited 48% in the presence of both antagonists
(p = 0.015), whereas antagonists alone were ineffective. The release of PEVs+ (2.4 ± 1.6 × 107/mL)
was unaffected by the P2Y1 antagonist, but was 62% inhibited by the P2Y12 antagonist (p = 0.035),
and 72% by both antagonists (p = 0.022). PEVs promoted coagulation in presence of tissue factor.
Conclusions: Inhibition of P2Y1 and P2Y12 receptors reduces platelet aggregation and affects the
release of distinct subpopulations of PEVs. Ticagrelor decreases the release of procoagulant PEVs from
activated platelets, which may contribute to the observed clinical benefits in patients treated with ticagrelor.

Abstract

Background: Activated platelets release platelet extracellular vesicles (PEVs). Adenosine diphosphate
(ADP) receptors P2Y1 and P2Y12 both play a role in platelet activation, The present hypothesis herein
is that the inhibition of these receptors may affect the release of PEVs.
Methods: Platelet-rich plasma from 10 healthy subjects was incubated with saline, P2Y1 antagonist
MRS2179 (100 μM), P2Y12 antagonist ticagrelor (1 μM), and a combination of both antagonists.
Platelets were activated by ADP (10 μM) under stirring conditions at 37°C. Platelet reactivity was
assessed by impedance aggregometry. Concentrations of PEVs– (positive for CD61 but negative for
P-selectin and phosphatidylserine) and PEVs+ (positive for all) were determined by a state-of-the-art
flow cytometer. Procoagulant activity of PEVs was measured by a fibrin generation test.
Results: ADP-induced aggregation (57 ± 13 area under curve {AUC] units) was inhibited 73%
by the P2Y1 antagonist, 86% by the P2Y12 antagonist, and 95% when combined (p < 0.001 for all).
The release of PEVs– (2.9 E ± 0.8 × 108/mL) was inhibited 48% in the presence of both antagonists
(p = 0.015), whereas antagonists alone were ineffective. The release of PEVs+ (2.4 ± 1.6 × 107/mL)
was unaffected by the P2Y1 antagonist, but was 62% inhibited by the P2Y12 antagonist (p = 0.035),
and 72% by both antagonists (p = 0.022). PEVs promoted coagulation in presence of tissue factor.
Conclusions: Inhibition of P2Y1 and P2Y12 receptors reduces platelet aggregation and affects the
release of distinct subpopulations of PEVs. Ticagrelor decreases the release of procoagulant PEVs from
activated platelets, which may contribute to the observed clinical benefits in patients treated with ticagrelor.

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Keywords

extracellular vesicles, platelets, ADP receptors, P2Y12 antagonists, ticagrelor

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About this article
Title

P2Y12 antagonist ticagrelor inhibits the release of procoagulant extracellular vesicles from activated platelets

Journal

Cardiology Journal

Issue

Vol 26, No 6 (2019)

Pages

782-789

Published online

2018-04-17

DOI

10.5603/CJ.a2018.0045

Pubmed

29671861

Bibliographic record

Cardiol J 2019;26(6):782-789.

Keywords

extracellular vesicles
platelets
ADP receptors
P2Y12 antagonists
ticagrelor

Authors

Aleksandra Gasecka
Rienk Nieuwland
Edwin van der Pol
Najat Hajji
Agata Ćwiek
Kinga Pluta
Michał Konwerski
Krzysztof J. Filipiak

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