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June 17, 2010British Journal of PharmacologyOpen Access

The roles and mechanisms of PAR4 and P2Y12/phosphatidylinositol 3‐kinase pathway in maintaining thrombin‐induced platelet aggregation

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Why the study?

Does combined inhibition of PAR4 and PI3K/P2Y12 pathways reduce the stability of thrombin-induced platelet aggregation in human platelets?

Population

Human platelets

Comparison

Inhibition of PAR4 and/or PI3K and/or P2Y12 vs Control

Design

Preclinical

Authors

CWChin‐Chung WuSWShih‐Yun WuCLChieh‐Yu Liao

Discussion

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Overview

May support dual antithrombotic targeting; hypothesis-generating in animal models and leaves open human translation.

Structured PICO

Does combined inhibition of PAR4 and PI3K/P2Y12 pathways reduce the stability of thrombin-induced platelet aggregation in human platelets?

P
Population
Human platelets
I
Intervention
Inhibition of PAR4 (YD-3) and/or PI3K (wortmannin) and/or P2Y12 (2-methylthioadenosine 5'-monophosphate triethylammonium salt)
C
Comparator
Control (uninhibited thrombin-stimulated platelets)
O
Outcome
Stability of thrombin-induced platelet aggregationsurrogate

PAR4 acts in parallel with the P2Y12/PI3K pathway to stabilize platelet aggregates, suggesting that dual inhibition may be a potential strategy for antithrombotic therapy.

Cite This Study

Wu et al. (2010) studied this question.

synapsesocial.com/papers/6a7d18c4469c795fc4278ca0https://doi.org/10.1111/j.1476-5381.2010.00921.x
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Also Consider

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

  1. 1Phosphoinositide 3-Kinase Inhibition Spares Actin Assembly in Activating Platelets but Reverses Platelet Aggregation1995 · 209 citations
  2. 2Coordinate Activation of Human Platelet Protease-activated Receptor-1 and -4 in Response to Subnanomolar α-Thrombin2008 · 23 citations
  3. 3A Key Role of Adenosine Diphosphate in the Irreversible Platelet Aggregation Induced by the PAR1-Activating Peptide Through the Late Activation of Phosphoinositide 3-Kinase1999 · 214 citations
  4. 4Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex2005 · 6,263 citations
  5. 5Phosphatidylinositol( , , ) -Trisphosphate Stimulates Phosphorylation of Pleckstrin in Human Platelets1995 · 56 citations