In vivo blockade of platelet ADP receptor P2Y(12) reduces embolus and thrombus formation but not thrombus stability

M.A. Gestel, van; J.W.M. Heemskerk; D.W. Slaaf; V.V.T. Heijnen; R.S. Reneman; M.G.A. Oude Egbrink

doi:10.1161/01.ATV.0000057809.32354.22

In vivo blockade of platelet ADP receptor P2Y(12) reduces embolus and thrombus formation but not thrombus stability

M.A. Gestel, van, J.W.M. Heemskerk, D.W. Slaaf, V.V.T. Heijnen, R.S. Reneman, M.G.A. Oude Egbrink

Research output: Contribution to journal › Article › Academic › peer-review

74 Citations (Scopus)

Abstract

Objective— ADP is a key platelet agonist in thromboembolism. One of the receptors involved in ADP-induced platelet activation is the P2Y12 receptor, which is a target for antithrombotic drugs. Methods and Results— Here, we present first evidence for a differential role of this receptor in thrombus and embolus formation in vivo. Anesthetized rabbits were treated with the selective P2Y12 antagonists AR-C69931 MX (3 µg · kg · min-1 IV) or clopidogrel (25 mg/kg orally). Efficacy of these treatments was monitored by aggregation and thrombin generation measurements in blood samples ex vivo. Mesenteric arterioles were mechanically injured; thrombus growth and subsequent embolus formation were visualized by real-time intravital microscopy. AR-C69931 MX and clopidogrel significantly (P

Original language	English
Pages (from-to)	518-523
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	23
Issue number	3
DOIs	https://doi.org/10.1161/01.ATV.0000057809.32354.22
Publication status	Published - 2003

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title = "In vivo blockade of platelet ADP receptor P2Y(12) reduces embolus and thrombus formation but not thrombus stability",

abstract = "Objective— ADP is a key platelet agonist in thromboembolism. One of the receptors involved in ADP-induced platelet activation is the P2Y12 receptor, which is a target for antithrombotic drugs. Methods and Results— Here, we present first evidence for a differential role of this receptor in thrombus and embolus formation in vivo. Anesthetized rabbits were treated with the selective P2Y12 antagonists AR-C69931 MX (3 µg · kg · min-1 IV) or clopidogrel (25 mg/kg orally). Efficacy of these treatments was monitored by aggregation and thrombin generation measurements in blood samples ex vivo. Mesenteric arterioles were mechanically injured; thrombus growth and subsequent embolus formation were visualized by real-time intravital microscopy. AR-C69931 MX and clopidogrel significantly (P",

author = "{Gestel, van}, M.A. and J.W.M. Heemskerk and D.W. Slaaf and V.V.T. Heijnen and R.S. Reneman and {Oude Egbrink}, M.G.A.",

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doi = "10.1161/01.ATV.0000057809.32354.22",

language = "English",

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T1 - In vivo blockade of platelet ADP receptor P2Y(12) reduces embolus and thrombus formation but not thrombus stability

AU - Gestel, van, M.A.

AU - Heemskerk, J.W.M.

AU - Slaaf, D.W.

AU - Heijnen, V.V.T.

AU - Reneman, R.S.

AU - Oude Egbrink, M.G.A.

PY - 2003

Y1 - 2003

N2 - Objective— ADP is a key platelet agonist in thromboembolism. One of the receptors involved in ADP-induced platelet activation is the P2Y12 receptor, which is a target for antithrombotic drugs. Methods and Results— Here, we present first evidence for a differential role of this receptor in thrombus and embolus formation in vivo. Anesthetized rabbits were treated with the selective P2Y12 antagonists AR-C69931 MX (3 µg · kg · min-1 IV) or clopidogrel (25 mg/kg orally). Efficacy of these treatments was monitored by aggregation and thrombin generation measurements in blood samples ex vivo. Mesenteric arterioles were mechanically injured; thrombus growth and subsequent embolus formation were visualized by real-time intravital microscopy. AR-C69931 MX and clopidogrel significantly (P

AB - Objective— ADP is a key platelet agonist in thromboembolism. One of the receptors involved in ADP-induced platelet activation is the P2Y12 receptor, which is a target for antithrombotic drugs. Methods and Results— Here, we present first evidence for a differential role of this receptor in thrombus and embolus formation in vivo. Anesthetized rabbits were treated with the selective P2Y12 antagonists AR-C69931 MX (3 µg · kg · min-1 IV) or clopidogrel (25 mg/kg orally). Efficacy of these treatments was monitored by aggregation and thrombin generation measurements in blood samples ex vivo. Mesenteric arterioles were mechanically injured; thrombus growth and subsequent embolus formation were visualized by real-time intravital microscopy. AR-C69931 MX and clopidogrel significantly (P

U2 - 10.1161/01.ATV.0000057809.32354.22

DO - 10.1161/01.ATV.0000057809.32354.22

M3 - Article

C2 - 12615691

SN - 1079-5642

VL - 23

SP - 518

EP - 523

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

IS - 3

ER -

In vivo blockade of platelet ADP receptor P2Y(12) reduces embolus and thrombus formation but not thrombus stability

Abstract

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