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September 1, 2018Arteriosclerosis Thrombosis and Vascular BiologyOpen Access

Impact of PI3Kα (Phosphoinositide 3-Kinase Alpha) Inhibition on Hemostasis and Thrombosis

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Key result

Absence or inhibition of PI3Kα resulted in a significant decrease in thrombus size and an increased time to arterial occlusion in mouse models, without modifying bleeding time.

Population

Mice selectively deficient in p110α in the megakaryocyte lineage and in vitro/ex vivo platelet models

Comparison

PI3Kα deficiency or isoform-selective PI3Kα… vs Wild-type mice or uninhibited controls

Design

Preclinical

Authors

PLPierre LaurentBHBéatrice HechlerRSRomain Solinhac

Discussion

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Overview

PI3Kα inhibition may offer antithrombotic benefit without bleeding liability in mice; leaves open translation to human therapy.

Structured PICO

P
Population
Mice selectively deficient in p110α in the megakaryocyte lineage and in vitro/ex vivo platelet models
I
Intervention
PI3Kα deficiency or isoform-selective PI3Kα inhibitors
C
Comparator
Wild-type mice or uninhibited controls
O
Outcome
Thrombus size after superficial injuries of mesenteric arteries and time to arterial occlusion after carotid lesionsurrogate

PI3Kα inhibition reduces arterial thrombosis in mouse models without increasing bleeding time, suggesting it may be a safe therapeutic target.

Cite This Study

Laurent et al. (2018) studied Arterial thrombosis. PI3Kα inhibition or deficiency vs. Control/Wild-type was evaluated on Thrombus size and time to arterial occlusion. Absence or inhibition of PI3Kα resulted in a significant decrease in thrombus size and an increased time to arterial occlusion in mouse models, without modifying bleeding time.

synapsesocial.com/papers/6a94331a2167e799456d346chttps://doi.org/10.1161/atvbaha.118.311410
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Also Consider

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

  1. 1Platelet PI3Kβ and GSK3 regulate thrombus stability at a high shear rate2014 · 88 citations
  2. 2Disrupting the platelet internal membrane via PI3KC2α inhibition impairs thrombosis independently of canonical platelet activation2020 · 34 citations
  3. 3Platelet PI3Kγ Contributes to Carotid Intima-Media Thickening under Severely Reduced Flow Conditions2015 · 7 citations
  4. 4Role of phosphoinositide 3-kinase β in platelet aggregation and thromboxane A2 generation mediated by Gi signalling pathways2010 · 100 citations
  5. 5Role of Phosphoinositide 3-Kinase β in Glycoprotein VI-mediated Akt Activation in Platelets2009 · 129 citations