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April 12, 2010PLoS ONEOpen Access

Stabilizing Role of Platelet P2Y12 Receptors in Shear-Dependent Thrombus Formation on Ruptured Plaques

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Key result

Inhibition or deficiency of platelet P2Y12 receptors significantly reduced thrombus size and increased embolization events on ruptured atherosclerotic plaques under high shear flow conditions.

Why the study?

Does P2Y12 inhibition with ticagrelor or cangrelor reduce thrombus size and improve stability on ruptured atherosclerotic plaques under high shear flow?

Population

Apoe-/- mice on C57BL/6 background fed a Western-type diet for 18-20 weeks, P2Y12-deficient mice, wild-type…

Comparison

P2Y12 inhibition via ticagrelor or cangrelor, or… vs Vehicle solution or wild-type/control conditions.

Design

Preclinical

Authors

RNReyhan Nergiz‐UnalJCJudith M.E.M. CosemansMFMarion A.H. Feijge

Discussion

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Overview

P2Y12 inhibition may alter thrombus dynamics on ruptured plaques; hypothesis-generating and should not change practice pending human data.

Structured PICO

Does P2Y12 inhibition with ticagrelor or cangrelor reduce thrombus size and improve stability on ruptured atherosclerotic plaques under high shear flow?

P
Population
In vivo and in vitro experimental models using Apoe-/- mice, P2Y12-deficient mice, and human blood to study thrombus formation on ruptured atherosclerotic plaques.
I
Intervention
P2Y12 inhibition via ticagrelor (in vivo: 420 mg/kg for 1 min, then 60 mg/kg/min for 15 min; in vitro: 20 µM) or cangrelor (in vivo: 3 mg/kg/min for 15 min; in vitro: 20 µM), or genetic P2Y12 deficiency.
C
Comparator
Vehicle solution (5% mannitol in saline) or wild-type/control conditions.
O
Outcome
Thrombus size and stability (number of embolization/disaggregation events) following acute plaque rupture or under flow conditions.surrogate

Main Result

p-value: p=<0.05

P2Y12 receptors play a crucial role in stabilizing thrombi on ruptured atherosclerotic plaques specifically under high shear flow conditions, providing mechanistic insight into the efficacy of P2Y12 inhibitors like ticagrelor.

Limitations

  • Other thrombogenic components have been identified in plaque material, including tissue factor, oxidized low density lipoproteins and lysophosphatidate, which were not fully isolated.

Cite This Study

Nergiz‐Unal et al. (2010) studied Atherothrombosis. P2Y12 inhibitors (ticagrelor and cangrelor) vs. Vehicle was evaluated on Thrombus size and stability (embolization events) (p=<0.05). Inhibition or deficiency of platelet P2Y12 receptors significantly reduced thrombus size and increased embolization events on ruptured atherosclerotic plaques under high shear flow conditions.

synapsesocial.com/papers/6a74fdb8756843cacbb1e055https://doi.org/10.1371/journal.pone.0010130
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries2003 · 352 citations
  2. 2P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries2003 · 25 citations
  3. 3Scientific and therapeutic insights into the role of the platelet P2Y12 receptor in thrombosis2003 · 77 citations
  4. 4Signaling via P2Y12 May Be Critical for Early Stabilization of Platelet Aggregates2014 · 12 citations
  5. 5Role of ADP Receptor P2Y<sub>12</sub>in Platelet Adhesion and Thrombus Formation in Flowing Blood2002 · 125 citations