P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries

André, Patrick; Delaney, Suzanne M.; LaRocca, Thomas J.; Vincent, D; DeGuzman, Francis; Jurek, Marzena; Koller, Beverly H.; Phillips, David R.; Conley, Pamela B.

doi:10.1172/jci17864

Cited by 305 publications

(213 citation statements)

References 47 publications

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“…Inhibition of AC by P2Y 12 may partly account for the more severe prolongation of the bleeding time in P2Y 12 knock-out mice, compared with P2Y 1 knock-outs [26][27][28][29]. This difference is apparently not explained by the respective role of P2Y 12 and P2Y 1 in platelet function as studied in vitro under several experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin

Cattaneo

Lecchi

2007

Journal of Thrombosis and Haemostasis

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Summary. Background: Activation of two receptors for adenosine diphosphate (ADP), P2Y 1 and P2Y 12 , is necessary for ADP-induced platelet aggregation (PA). It is generally believed that the antithrombotic effects of drugs inhibiting P2Y 12 , such as clopidogrel, are uniquely mediated by inhibition of P2Y 12 -dependent PA. However, as P2Y 12 is negatively coupled to adenylyl cyclase (AC), its inhibition may also exert antithrombotic effects through the potentiation of prostacyclin (PGI 2 ), which inhibit PA by stimulating AC. Objectives: To test whether inhibition of P2Y 12 potentiates the antiplatelet effects of PGI 2 . Methods: We measured the effects of PGI 2 (0.01-10 lM) on PA of washed human platelets induced by thrombin (0.5 U mL )1 ) in the presence or absence of ARC69931MX (anti-P2Y 12 ) or MRS2500 (anti-P2Y 1 ). Results: PGI 2 inhibited PA in the presence of anti-P2Y 12 , but not in the presence of anti-P2Y 1 or in the absence of inhibitors. In contrast, dibutyrylcyclicAMP inhibited PA both in the presence and absence of anti-P2Y 1 or anti-P2Y 12 . PGI 2 increased platelet cyclicAMP levels only in the absence of thrombin or in the presence of thrombin plus anti-P2Y 12 . Conclusions: PGI 2 did not inhibit PA induced by thrombin, because its effect on AC was prevented by released ADP interacting with P2Y 12 . Anti-P2Y 12 drugs, by rescuing AC activity, potentiate the antiplatelet effect of PGI 2 , which may contribute to their antithrombotic effect.

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Section: Discussionmentioning

confidence: 99%

Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin

Cattaneo

Lecchi

2007

Journal of Thrombosis and Haemostasis

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“…These data support the hypothesized function of the P2Y 1 receptor as being necessary for the initiation of platelet aggregation, and the P2Y 12 receptor for maintenance of aggregation (21) . However, as described for P2Y 1 (22,23) and P2Y 12 (24) knockout mouse models, the lack of either receptor does still allow for a small aggregation response. In line with this model, we obtained similar results in light scatter experiments (Supplementary Figure 6 ).…”

Section: Quantitative Characterization Of Platelet P2 Receptors By Lamentioning

confidence: 99%

Low angle light scattering analysis: a novel quantitative method for functional characterization of human and murine platelet receptors

Mindukshev

Gambaryan

Kehrer

et al. 2011

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background: Determinations of platelet receptor functions are indispensable diagnostic indicators of cardiovascular and hemostatic diseases including hereditary and acquired receptor defects and receptor responses to drugs. However, presently available techniques for assessing platelet function have some disadvantages, such as low sensitivity and the requirement of large sample sizes and unphysiologically high agonist concentrations. Our goal was to develop and initially characterize a new technique designed to quantitatively analyze platelet receptor activation and platelet function on the basis of measuring changes in low angle light scattering. Methods: We developed a novel technique based on low angle light scattering registering changes in light scattering at a range of different angles in platelet suspensions during activation. Results: The method proved to be highly sensitive for simultaneous real time detection of changes in size and shape of platelets during activation. Unlike commonly-used methods, the

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“…Activation of both P2Y 1 and P2Y 12 receptors is necessary for sustained ADP-induced platelet aggregation [13,14]. The success of the P2Y 12 receptor as a therapeutic target relates to its central role in the potentiation of dense granule secretion, platelet aggregation, pro-coagulant activity and overall thrombus growth and stability [14][15][16][17].…”

Section: Atherothrombosis and The Role Of The Platelet P2y 12 Receptormentioning

confidence: 99%

Cangrelor for the management and prevention of arterial thrombosis

Storey

Sinha

2016

Expert Review of Cardiovascular Therapy

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SUMMARYCangrelor is an intravenous, reversibly-binding platelet P2Y 12 receptor antagonist with ultra-rapid onset and offset of action. It is approved in Europe and United States for use in patients undergoing percutaneous coronary intervention, a setting in which it has proven superiority to initial treatment with clopidogrel. Preliminary clinical evidence suggests it would also be a favourable option in bridging patients from discontinuation of oral antiplatelet therapy to the time of major surgery. This review describes the background for the development of cangrelor, the biology, pharmacology and clinical evidence supporting its use, and its likely position in the future.

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P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries

Cited by 305 publications

References 47 publications

Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin

Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin

Low angle light scattering analysis: a novel quantitative method for functional characterization of human and murine platelet receptors

Cangrelor for the management and prevention of arterial thrombosis

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